The DOI matches its Crossref record; 221 of the 221 references it cites were found in a registry or an index; none of the 226 sources its claims cite is checked for support yet.
Cellular mechanisms of tumour suppression by the retinoblastoma gene
Open accessAbstract
The retinoblastoma (RB) tumour suppressor gene is functionally inactivated in a broad range of paediatric and adult cancers, and a plethora of cellular functions and partners have been identified for the RB protein. Data from human tumours and studies from mouse models indicate that loss of RB function contributes to both cancer initiation and progression. However, we still do not know the identity of the cell types in which RB normally prevents cancer initiation in vivo, and the specific functions of RB that suppress distinct aspects of the tumorigenic process are poorly understood.
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In the paper
“mouse genetic studies have confirmed that RB is crucial in preventing the initiation of this lung cancer sub-type24”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation
What the sources say
- Not checked yetcites [24] Meuwissen, R. et al. Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model. Cancer Cell 4, 181–189 (2003). Describes a mouse model of human SCLC, the only adult tumour type in which loss of RB function occurs in most, if not all cases. source
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“Whereas p130, rather than RB, binds to the promoters of genes in G0 cells28–30”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation > Loss of RB function and cell cycle re-entry in quiescent stem cells.
What the sources say
- Not checked yetcites [28] Smith, E. J., Leone, G., DeGregori, J., Jakoi, L. & Nevins, J. R. The accumulation of an E2F-p130 transcriptional repressor distinguishes a G0 cell state from a G1 cell state. Mol. Cell. Biol. 16, 6965–6976 (1996). source
- Not checked yetcites [29] Balciunaite, E. et al. Pocket protein complexes are recruited to distinct targets in quiescent and proliferating cells. Mol. Cell. Biol. 25, 8166–8178 (2005). source
- Not checked yetcites [30] Takahashi, Y., Rayman, J. B. & Dynlacht, B. D. Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression. Genes Dev. 14, 804–816 (2000). source
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In the paper
“upstream regulators of RB have been involved in cancer initiation in patients, both in familial and sporadic cases, and in several organs and tissues25–27.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation
What the sources say
- Not checked yetcites [25] Ranade, K. et al. Mutations associated with familial melanoma impair p16INK4 function. Nature Genet. 10, 114–116 (1995). source
- Not checked yetcites [26] Zuo, L. et al. Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nature Genet. 12, 97–99 (1996). source
- Not checked yetcites [27] Berman, H. et al. Genetic and epigenetic changes in mammary epithelial cells identify a subpopulation of cells involved in early carcinogenesis. Cold Spring Harb. Symp. Quant. Biol. 70, 317–327 (2005). source
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In the paper
“the high penetrance of pituitary and thyroid tumours in Rb+/− mice and the development of other tumours in mice that have been subjected to tissue-specific Rb deletion using the Cre–lox system demonstrate that loss of Rb is a causal event in many cancer types7.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation
What the sources say
- Not checked yetcites [7] Wikenheiser-Brokamp, K. A. Retinoblastoma family proteins: insights gained through genetic manipulation of mice. Cell Mol. Life Sci. 63, 767–780 (2006). source
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In the paper
“Furthermore, RB is also an adaptor protein that recruits chromatin remodelling enzymes to control the expression of specific target genes and to modify chromatin structure at a chromosome-wide level13,14”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Abstract
What the sources say
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In the paper
“human papillomavirus (HPV) is thought to initiate cervical carcinoma and squamous cell carcinoma of the head and neck in part by inactivating RB through expression of the E7 oncoprotein21,22”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation
What the sources say
- Not checked yetcites [21] Doorbar, J. Molecular biology of human papillomavirus infection and cervical cancer. Clin. Sci. 110, 525–541 (2006). source
- Not checked yetcites [22] Perez-Ordonez, B., Beauchemin, M. & Jordan, R. C. Molecular biology of squamous cell carcinoma of the head and neck. J. Clin. Pathol. 59, 445–453 (2006). source
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In the paper
“Loss of RB also increases the risk of osteosarcoma development in children and teenagers18–20.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation
What the sources say
- Not checked yetcites [18] Friend, S. H. et al. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323, 643–646 (1986). source
- Not checked yetcites [19] Bookstein, R. & Lee, W. H. Molecular genetics of the retinoblastoma suppressor gene. Crit. Rev. Oncog. 2, 211–227 (1991).
- Not checked yetcites [20] Deshpande, A. & Hinds, P. W. The retinoblastoma protein in osteoblast differentiation and osteosarcoma. Curr. Mol. Med. 6, 809–817 (2006).
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In the paper
“RB is inactivated in more than 90% of human small-cell lung carcinomas (SCLC)”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation
What the sources say
- Not checked yetcites [24] Meuwissen, R. et al. Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model. Cancer Cell 4, 181–189 (2003). Describes a mouse model of human SCLC, the only adult tumour type in which loss of RB function occurs in most, if not all cases. source
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In the paper
“In Arabidopsis roots, loss of the RB homologue RBR leads to expansion of stem cells in the stem cell pool, seemingly without affecting their self-renewal potential and their proliferative status but by preventing their differentiation36.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation > Loss of RB function and cell cycle re-entry in quiescent stem cells.
What the sources say
- Not checked yetcites [36] Wildwater, M. et al. The RETINOBLASTOMA-RELATED gene regulates stem cell maintenance in Arabidopsis roots. Cell 123, 1337–1349 (2005). Provides the first description of a role for RB in maintaining a stem cell pool in vivo. source
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In the paper
“loss of Rb results in cell cycle re-entry in mature hepatocytes43.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation > Cell cycle re-entry in post-mitotic differentiated cells mutant for RB function.
What the sources say
- Not checked yetcites [43] Mayhew, C. N. et al. Liver-specific pRB loss results in ectopic cell cycle entry and aberrant ploidy. Cancer Res. 65, 4568–4577 (2005). source
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In the paper
“RB is now viewed as a transcriptional co-factor that can bind to and either antagonize or potentiate the function of numerous transcription factors11,12.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Abstract
What the sources say
- Not checked yetcites [11] Morris, E. J. & Dyson, N. J. Retinoblastoma protein partners. Adv. Cancer Res. 82, 1–54 (2001). source
- Not checked yetcites [12] Macaluso, M., Montanari, M. & Giordano, A. Rb family proteins as modulators of gene expression and new aspects regarding the interaction with chromatin remodeling enzymes. Oncogene 25, 5263–5267 (2006). source
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In the paper
“it is well-accepted that loss of RB is the initiating event in these familial retinal tumours, as well as in sporadic cases15–17.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation
What the sources say
- Not checked yetcites [15] Knudson, A. G., Jr. Genetic predisposition to cancer. Cancer Detect Prev. 7, 1–8 (1984).
- Not checked yetcites [16] Corson, T. W. & Gallie, B. L. One hit, two hits, three hits, more? Genomic changes in the development of retinoblastoma. Genes Chromosomes Cancer 46, 617–634 (2007). source
- Not checked yetcites [17] Dimaras, H. et al. Loss of RB1 induces non-proliferative retinoma; increasing genomic instability correlates with progression to retinoblastoma. Hum. Mol. Genet. (2008). source
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In the paper
“Recent studies have also demonstrated that control of the stability of the p27 cell cycle inhibitor (which is encoded by CDKN1B) by RB, through the interaction of RB with the anaphase-promoting complex/cyclosome (APC/C), is an important part of the capacity of RB to arrest cells in G1; therefore, E2Fs are not the sole mediators of the capacity of RB to control the G1–S transition5,6.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Abstract
What the sources say
- Not checked yetcites [5] Ji, P. et al. An Rb–Skp2–p27 pathway mediates acute cell cycle inhibition by Rb and is retained in a partial-penetrance Rb mutant. Mol. Cell 16, 47–58 (2004). source
- Not checked yetcites [6] Binne, U. K. et al. Retinoblastoma protein and anaphase-promoting complex physically interact and functionally cooperate during cell-cycle exit. Nature Cell Biol. 9, 225–232 (2007). References 5 and 6 demonstrate that the role of RB in cell cycle control is not solely mediated through its interactions with E2F transcription factors. source
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In the paper
“In mammalian cells, RB belongs to a family of three proteins that also includes p107 and p130, which are structurally and functionally related to RB and belong to the same cellular pathway, but display distinct functions from RB in specific contexts4,7–10”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Abstract
What the sources say
- Not checked yetcites [4] Dannenberg, J. H. & te Riele, H. P. The retinoblastoma gene family in cell cycle regulation and suppression of tumorigenesis. Results Probl. Cell Differ. 42, 183–225 (2006). source
- Not checked yetcites [7] Wikenheiser-Brokamp, K. A. Retinoblastoma family proteins: insights gained through genetic manipulation of mice. Cell Mol. Life Sci. 63, 767–780 (2006). source
- Not checked yetcites [8] Cobrinik, D. Pocket proteins and cell cycle control. Oncogene 24, 2796–2809 (2005). source
- Not checked yetcites [9] Claudio, P. P., Tonini, T. & Giordano, A. The retinoblastoma family: twins or distant cousins? Genome Biol. 3, reviews3012 (2002). source
- Not checked yetcites [10] Classon, M. & Dyson, N. p107 and p130: versatile proteins with interesting pockets. Exp. Cell Res. 264, 135–147. (2001). source
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In the paper
“It is now believed that RB has many cellular roles in addition to serving as a G1 checkpoint, including control of cellular differentiation during embryogenesis and in adult tissues, regulation of apoptotic cell death, maintenance of permanent cell cycle arrest and preservation of chromosomal stability3,4.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Abstract
What the sources say
- Not checked yetcites [3] Zheng, L. & Lee, W. H. The retinoblastoma gene: a prototypic and multifunctional tumor suppressor. Exp. Cell Res. 264, 2–18 (2001). source
- Not checked yetcites [4] Dannenberg, J. H. & te Riele, H. P. The retinoblastoma gene family in cell cycle regulation and suppression of tumorigenesis. Results Probl. Cell Differ. 42, 183–225 (2006). source
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In the paper
“in HPV-induced cervical cancers, the virus initiates cancer in dividing cells in the basal layer of the epithelium, preventing their normal cell cycle exit and maturation21.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation > Loss of RB function in cycling progenitor cells and differentiating cells.
What the sources say
- Not checked yetcites [21] Doorbar, J. Molecular biology of human papillomavirus infection and cervical cancer. Clin. Sci. 110, 525–541 (2006). source
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In the paper
“RB has also been shown to participate in and potentially modulate the structure and location of heterochromatin formation in senescent cells40”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation > Cell cycle re-entry in post-mitotic differentiated cells mutant for RB function.
What the sources say
- Not checked yetcites [40] Narita, M. et al. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 113, 703–716 (2003). source
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In the paper
“In these cells, loss of RB might accelerate proliferation and prevent normal cell cycle exit in G1, which is associated with differentiation”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation > Loss of RB function in cycling progenitor cells and differentiating cells.
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In the paper
“In muscle cells, loss of Rb function can result in no cell cycle re-entry45,46 or in cell cycle re-entry followed by a block in G2 (REF. 47), depending on the culture conditions.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation > Cell cycle re-entry in post-mitotic differentiated cells mutant for RB function.
What the sources say
- Not checked yetcites [45] Camarda, G. et al. A pRb-independent mechanism preserves the postmitotic state in terminally differentiated skeletal muscle cells. J. Cell Biol. 167, 417–423 (2004). source
- Not checked yetcites [46] Huh, M. S., Parker, M. H., Scime, A., Parks, R. & Rudnicki, M. A. Rb is required for progression through myogenic differentiation but not maintenance of terminal differentiation. J. Cell Biol. 166, 865–876 (2004). source
- Not checked yetcites [47] Blais, A., van Oevelen, C. J., Margueron, R., Acosta-Alvear, D. & Dynlacht, B. D. Retinoblastoma tumor suppressor protein-dependent methylation of histone H3 lysine 27 is associated with irreversible cell cycle exit. J. Cell Biol. 179, 1399–1412 (2007). source
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In the paper
“Rb inactivation in mouse retinal progenitors results in cell-autonomous defects in cell cycle exit, specific differentiation defects, proliferation in differentiating cells and increased cell death.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation > Loss of RB function in cycling progenitor cells and differentiating cells.
What the sources say
- Not checked yetcites [50] Chen, D. et al. Cell-specific effects of RB or RB/p107 loss on retinal development implicate an intrinsically death-resistant cell-of-origin in retinoblastoma. Cancer Cell 5, 539–551 (2004). source
- Not checked yetcites [51] MacPherson, D. et al. Cell type-specific effects of Rb deletion in the murine retina. Genes Dev. 18, 1681–1694 (2004). source
- Not checked yetcites [55] Zhang, J. et al. Rb regulates proliferation and rod photoreceptor development in the mouse retina. Nature Genet. 36, 351–360 (2004). source
- Not checked yetcites [56] Dyer, M. A. & Bremner, R. The search for the retinoblastoma cell of origin. Nature Rev. Cancer 5, 91–101 (2005). source
- Not checked yetcites [57] Pacal, M. & Bremner, R. Insights from animal models on the origins and progression of retinoblastoma. Curr. Mol. Med. 6, 759–781 (2006). References 50, 51 and 55, and the two reviews 56 and 57 describe the first breedable mouse models of retinoblastoma and investigate the mechanisms of tumorigenesis in the retina.
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In the paper
“In the cochlea, Rb deletion allows increased proliferation of precursor cells, and although mature mechanosensory hair cells are capable of re-entering the cell cycle, they fail to complete cellular division48.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation > Cell cycle re-entry in post-mitotic differentiated cells mutant for RB function.
What the sources say
- Not checked yetcites [48] Weber, T. et al. Rapid cell-cycle reentry and cell death after acute inactivation of the retinoblastoma gene product in postnatal cochlear hair cells. Proc. Natl Acad. Sci. USA 105, 781–785 (2008). source
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In the paper
“In the brain, RB levels increase as progenitor cells normally undergo cell cycle exit and loss of Rb results in delayed cell cycle exit in these cells44,49,53,54.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation > Loss of RB function in cycling progenitor cells and differentiating cells.
What the sources say
- Not checked yetcites [44] Slack, R. S., El-Bizri, H., Wong, J., Belliveau, D. J. & Miller, F. D. A critical temporal requirement for the retinoblastoma protein family during neuronal determination. J. Cell Biol. 140, 1497–1509 (1998). source
- Not checked yetcites [49] Ferguson, K. L. et al. Telencephalon-specific Rb knockouts reveal enhanced neurogenesis, survival and abnormal cortical development. EMBO J. 21, 3337–3346. (2002). source
- Not checked yetcites [53] Callaghan, D. A. et al. Neural precursor cells differentiating in the absence of Rb exhibit delayed terminal mitosis and deregulated E2F 1 and 3 activity. Dev. Biol. 207, 257–270 (1999). source
- Not checked yetcites [54] Ferguson, K. L. & Slack, R. S. The Rb pathway in neurogenesis. Neuroreport 12, A55–A62 (2001). source
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In the paper
“Therefore, cell cycle re-entry in terminally differentiated cells owing to loss of RB function might be context-dependent and most of the time insufficient to initiate cancer.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation > Cell cycle re-entry in post-mitotic differentiated cells mutant for RB function.
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In the paper
“RB promotes the differentiation of multiple lineages by binding and regulating tissue-specific transcription factors11,42 and inhibitors of differentiation such as ID2 and EID1 (REFS 62–65), as well as general transcription factors and chromatin modifiers66,67.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation > Loss of RB function in cycling progenitor cells and differentiating cells.
What the sources say
- Not checked yetcites [11] Morris, E. J. & Dyson, N. J. Retinoblastoma protein partners. Adv. Cancer Res. 82, 1–54 (2001). source
- Not checked yetcites [42] Skapek, S. X., Pan, Y. R. & Lee, E. Y. Regulation of cell lineage specification by the retinoblastoma tumor suppressor. Oncogene 25, 5268–5276 (2006). source
- Not checked yetcites [62] Iavarone, A. et al. Retinoblastoma promotes definitive erythropoiesis by repressing Id2 in fetal liver macrophages. Nature 432, 1040–1045 (2004). source
- Not checked yetcites [63] Lasorella, A., Noseda, M., Beyna, M., Yokota, Y. & Iavarone, A. Id2 is a retinoblastoma protein target and mediates signalling by Myc oncoproteins. Nature 407, 592–598 (2000). Describes a crucial link between MYC signalling and RB function, and provides mechanistic evidence that the interactions between ID2 and RB might regulate the proliferation and differentiation of cells. source
- Not checked yetcites [64] Miyake, S. et al. Cells degrade a novel inhibitor of differentiation with E1A-like properties upon exiting the cell cycle. Mol. Cell. Biol. 20, 8889–8902 (2000). source
- Not checked yetcites [65] MacLellan, W. R., Xiao, G., Abdellatif, M. & Schneider, M. D. A novel Rb- and p300-binding protein inhibits transactivation by MyoD. Mol. Cell. Biol. 20, 8903–8915 (2000). source
- Not checked yetcites [66] Benevolenskaya, E. V., Murray, H. L., Branton, P., Young, R. A. & Kaelin, W. G., Jr. Binding of pRB to the PHD protein RBP2 promotes cellular differentiation. Mol. Cell 18, 623–635 (2005). source
- Not checked yetcites [67] Krutzfeldt, M. et al. Selective ablation of retinoblastoma protein function by the RET finger protein. Mol. Cell 18, 213–224 (2005). source
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In the paper
“Rb-mutant HSCs that are induced to enter the cell cycle under conditions that induce cellular stress might not be able to properly re-enter a quiescent state and can undergo enforced differentiation32–34.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer initiation > Loss of RB function and cell cycle re-entry in quiescent stem cells.
What the sources say
- Not checked yetcites [32] Daria, D. et al. The retinoblastoma tumor suppressor is a critical intrinsic regulator for hematopoietic stem and progenitor cells under stress. Blood 111, 1894–1902 (2008). source
- Not checked yetcites [33] Walkley, C. R. & Orkin, S. H. Rb is dispensable for self-renewal and multilineage differentiation of adult hematopoietic stem cells. Proc. Natl Acad. Sci. USA 103, 9057–9062 (2006). source
- Not checked yetcites [34] Walkley, C. R., Shea, J. M., Sims, N. A., Purton, L. E. & Orkin, S. H. Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment. Cell 129, 1081–1095 (2007). source
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In the paper
“In these hepatocytes, E2F activity has been shown to activate Ddb2 (damage-specific DNA binding 2), a gene that is crucial for DNA repair, and loss of RB might therefore increase the DNA repair activity of mutant cells82.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > RB retention and early cancer progression > Loss of RB function increases cell death and DNA repair.
What the sources say
- Not checked yetcites [82] Prost, S., Lu, P., Caldwell, H. & Harrison, D. E2F regulates DDB2: consequences for DNA repair in Rb-deficient cells. Oncogene 26, 3572–3581 (2007). source
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In the paper
“In normal adult hepatocytes, which are often tetraploid, acute deletion of Rb results in cell cycle re-entry and increased aneuploidy43.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer progression > Loss of RB results in chromosomal instability.
What the sources say
- Not checked yetcites [43] Mayhew, C. N. et al. Liver-specific pRB loss results in ectopic cell cycle entry and aberrant ploidy. Cancer Res. 65, 4568–4577 (2005). source
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In the paper
“DNA damage increases the acetylation of human RB at lysines 873 and 874, which decreases RB phosphorylation by cyclin–Cdk (cyclin-dependent kinase) complexes and therefore increases its repression over E2F1 (REF. 77).”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > RB retention and early cancer progression > Loss of RB function increases cell death and DNA repair.
What the sources say
- Not checked yetcites [77] Markham, D., Munro, S., Soloway, J., O'Connor, D. P. & La Thangue, N. B. DNA-damage-responsive acetylation of pRb regulates binding to E2F-1. EMBO Rep. 7, 192–198 (2006). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In Rb-deficient cells, UV-induced lesions fail to induce cell cycle arrest, unlike in Rb wild-type cells; however, DNA repair mechanisms are rapidly engaged81.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > RB retention and early cancer progression > Loss of RB function increases cell death and DNA repair.
What the sources say
- Not checked yetcites [81] Bosco, E. E. & Knudsen, E. S. Differential role of RB in response to UV and IR damage. Nucleic Acids Res. 33, 1581–1592 (2005). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Strikingly, these transgenic mice develop focal hyperplastic lesions and mammary tumours, probably because the survival of differentiated mammary epithelial cells is extended after pregnancy86.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > RB retention and early cancer progression > Loss of RB function increases cell death and DNA repair.
What the sources say
- Not checked yetcites [86] Jiang, Z. & Zacksenhaus, E. Activation of retinoblastoma protein in mammary gland leads to ductal growth suppression, precocious differentiation, and adenocarcinoma. J. Cell Biol. 156, 185–198 (2002). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The idea that RB could promote cancer under certain conditions by increasing survival is supported by experiments in transgenic mice expressing a phosphorylation-resistant, constitutively active allele of Rb in the mammary gland epithelium.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > RB retention and early cancer progression > Loss of RB function increases cell death and DNA repair.
What the sources say
- Not checked yetcites [86] Jiang, Z. & Zacksenhaus, E. Activation of retinoblastoma protein in mammary gland leads to ductal growth suppression, precocious differentiation, and adenocarcinoma. J. Cell Biol. 156, 185–198 (2002). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the presence of RB in tumour cells could in theory promote their differentiation and thereby restrict their proliferative potential, which might explain why RB must be lost during the progression from a well differentiated to a poorly differentiated tumour.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer progression > Loss of RB might decrease the differentiation potential of mutant cells.
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Both decreased INK4A and presence of E1A result in inhibition of protein interactions that are mediated through the RB pocket region, suggesting the structure and/or specific modifications of RB might distinctly regulate individual functions”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > RB retention and early cancer progression > Loss of RB function increases cell death and DNA repair.
What the sources say
- Not checked yetcites [92] Seifried, L. A. et al. pRB-E2F1 complexes are resistant to adenovirus E1A-mediated disruption. J. Virol. 82, 4511–4520 (2008). source
- Not checked yetcites [94] Pickering, M. T. & Kowalik, T. F. Rb inactivation leads to E2F1-mediated DNA double-strand break accumulation. Oncogene 25, 746–755 (2006). source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“It has been suggested that this type of chromosomal instability is linked to the progression of benign eye lesions to malignant retinoblastoma17.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer progression > Loss of RB results in chromosomal instability.
What the sources say
- Not checked yetcites [17] Dimaras, H. et al. Loss of RB1 induces non-proliferative retinoma; increasing genomic instability correlates with progression to retinoblastoma. Hum. Mol. Genet. (2008). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“the vast majority of tumour types only display RB alterations later in tumour progression (TABLE 1) and that patients with familial retinoblastoma are not strongly predisposed to a wide variety of other tumours73.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > RB retention and early cancer progression
What the sources say
- Not checked yetcites [73] Kleinerman, R. A. et al. Risk of new cancers after radiotherapy in long-term survivors of retinoblastoma: an extended follow-up. J. Clin. Oncol. 23, 2272–2279 (2005). source
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Wild-type RB activity might normally slow down the proliferation of tumour cells by acting as a checkpoint not only at the G1–S transition but also during S phase and at the G2–M transition, and loss of this checkpoint could contribute to the ability of a tumour cell to proliferate in the presence of genomic abnormalities.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer progression > Loss of RB results in chromosomal instability.
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Autophagy, which is induced in hypoxic conditions, can initially allow survival of a hypoxic cell by enabling metabolism to continue; however, extended autophagy can eventually result in cell death95.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > RB retention and early cancer progression > Loss of RB function increases autophagy in response to hypoxia.
What the sources say
- Not checked yetcites [95] Mathew, R., Karantza-Wadsworth, V. & White, E. Role of autophagy in cancer. Nature Rev. Cancer 7, 961–967 (2007). source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“it is possible that functional inactivation of RB by phosphorylation or by viral oncoproteins does not induce the same amount of cell death as deletion of RB, potentially explaining why mutations in upstream members of the pathway are selected in some cancers92,93.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > RB retention and early cancer progression > Loss of RB function increases cell death and DNA repair.
What the sources say
- Not checked yetcites [92] Seifried, L. A. et al. pRB-E2F1 complexes are resistant to adenovirus E1A-mediated disruption. J. Virol. 82, 4511–4520 (2008). source
- Not checked yetcites [93] Weinstein, I. B. Disorders in cell circuitry during multistage carcinogenesis: the role of homeostasis. Carcinogenesis 21, 857–864 (2000). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Double-strand breaks activate the kinases ATM (ataxia telangiectasia mutated) and CHK2 (checkpoint homologue 2), which phosphorylates RB at serine 612, resulting in the formation of a RB–E2F1 complex that can inhibit E2F1-specific target genes that are necessary for apoptosis, such as Apaf1 and Trp73 (REF. 76).”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > RB retention and early cancer progression > Loss of RB function increases cell death and DNA repair.
What the sources say
- Not checked yetcites [76] Inoue, Y., Kitagawa, M. & Taya, Y. Phosphorylation of pRB at Ser612 by Chk1/2 leads to a complex between pRB and E2F-1 after DNA damage. EMBO J. 26, 2083–2093 (2007). source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“mutations in RB might participate in this phenotype by inducing defects during DNA replication and abnormal chromosomal segregation in mitosis101–103, which could result in abnormal expression of other cancer genes, enabling tumour progression.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer progression > Loss of RB results in chromosomal instability.
What the sources say
- Not checked yetcites [101] Foijer, F., Wolthuis, R. M., Doodeman, V., Medema, R. H. & te Riele, H. Mitogen requirement for cell cycle progression in the absence of pocket protein activity. Cancer Cell 8, 455–466 (2005). source
- Not checked yetcites [102] Eguchi, T., Takaki, T., Itadani, H. & Kotani, H. RB silencing compromises the DNA damage-induced G2/M checkpoint and causes deregulated expression of the ECT2 oncogene. Oncogene 26, 509–520 (2007). source
- Not checked yetcites [103] Kennedy, B. K., Barbie, D. A., Classon, M., Dyson, N. & Harlow, E. Nuclear organization of DNA replication in primary mammalian cells. Genes Dev. 14, 2855–2868 (2000). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Through these mechanisms, the presence of RB in tumour cells might prevent E2F-mediated apoptosis in response to DNA damage, and might prevent the elimination of tumour cells.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > RB retention and early cancer progression > Loss of RB function increases cell death and DNA repair.
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“among the E2F family, induction of apoptosis is a function largely mediated by E2F1 and its repression is mediated by specific RB and E2F1 protein domains that are distinct from those through which RB interacts with E2F1, E2F2, E2F3 and E2F4 to control cell cycle progression78.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > RB retention and early cancer progression > Loss of RB function increases cell death and DNA repair.
What the sources say
- Not checked yetcites [78] Dick, F. A. Structure-function analysis of the retinoblastoma tumor suppressor protein — is the whole a sum of its parts? Cell Div. 2, 26 (2007). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“So, similar to apoptosis, loss of RB might increase autophagy-mediated cell death, and presence of RB might be beneficial to early tumours under some conditions”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > RB retention and early cancer progression > Loss of RB function increases autophagy in response to hypoxia.
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Both chromatin remodelling and DNA methylation have been linked to tumorigenesis119,120.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer progression > Loss of RB results in chromosomal instability.
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“DNA methyltransferase DNMT1, which is both an E2F target112 and a RB–E2F protein binding partner118, has been shown to be upregulated in human cancers and in response to loss of RB.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer progression > Loss of RB results in chromosomal instability.
What the sources say
- Not checked yetcites [112] McCabe, M. T., Davis, J. N. & Day, M. L. Regulation of DNA methyltransferase 1 by the pRb/E2F1 pathway. Cancer Res. 65, 3624–3632 (2005). source
- Not checked yetcites [118] Robertson, K. D. et al. DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters. Nature Genet. 25, 338–342 (2000). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Many chromatin modifiers bind to RB through the LXCXE binding domain (BOX 2), and recent evidence has demonstrated that an LXCXE mutant that retains E2F-binding capability, and therefore has no effect on MAD2 levels, still contributes to chromosome missegregation and genomic instability through its failure to regulate appropriate pericentric heterochromatin formation109.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer progression > Loss of RB results in chromosomal instability.
What the sources say
- Not checked yetcites [109] Isaac, C. E. et al. The retinoblastoma protein regulates pericentric heterochromatin. Mol. Cell. Biol. 26, 3659–3671 (2006). Describes one of the first in vivo models to use a knock-in mouse to understand the cellular function of individual protein residues of RB. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“MAD2 levels are increased in Rb-deficient cells, correlating with increased levels of activating E2F, and overexpression of MAD2 is sufficient to induce aneuploidy and tumour formation in transgenic mice108.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer progression > Loss of RB results in chromosomal instability.
What the sources say
- Not checked yetcites [108] Sotillo, R. et al. Mad2 overexpression promotes aneuploidy and tumorigenesis in mice. Cancer Cell 11, 9–23 (2007). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These epigenetic changes might result in abnormal inactivation of tumour suppressors and activation of oncogenes without the physical mutation of these genes.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer progression > Loss of RB results in chromosomal instability.
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Through this pathway, the presence of RB leads to downregulation of SKP2 and therefore stabilization of p27, which inhibits cyclin-E-associated kinase activity129.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer progression > Loss of RB prevents induction of cellular senescence.
What the sources say
- Not checked yetcites [129] Alexander, K. & Hinds, P. W. Requirement for p27(KIP1) in retinoblastoma protein-mediated senescence. Mol. Cell. Biol. 21, 3616–3631 (2001). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“So, although loss of RB might not be sufficient to trigger a full angiogenic response, it might participate in this crucial stage of tumour progression in vivo.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer progression > Loss of RB promotes angiogenesis.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
- Rests on an assumption: Tumours acquire mutations that enhance endothelial cell recruitment and new blood vessel formation to overcome hypoxia.
None of the sources cited for this claim have been checked yet.
In the paper
“Rb-deficient cells fail to properly arrest in G1 upon DNA damage and might replicate mutated DNA, leading to the accumulation of mutations102,105,111,116.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer progression > Loss of RB results in chromosomal instability.
What the sources say
- Not checked yetcites [102] Eguchi, T., Takaki, T., Itadani, H. & Kotani, H. RB silencing compromises the DNA damage-induced G2/M checkpoint and causes deregulated expression of the ECT2 oncogene. Oncogene 26, 509–520 (2007). source
- Not checked yetcites [105] Zheng, L. & Lee, W. H. Retinoblastoma tumor suppressor and genome stability. Adv. Cancer Res. 85, 13–50 (2002). source
- Not checked yetcites [111] Knudsen, E. S., Sexton, C. R. & Mayhew, C. N. Role of the retinoblastoma tumor suppressor in the maintenance of genome integrity. Curr. Mol. Med. 6, 749–757 (2006).
- Not checked yetcites [116] Harrington, E. A., Bruce, J. L., Harlow, E. & Dyson, N. pRB plays an essential role in cell cycle arrest induced by DNA damage. Proc. Natl Acad. Sci. USA 95, 11945–11950 (1998). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“A clear example that RB and p16 mutations are not equivalent comes from the observations that RB is mutated in most, if not all cases of SCLC, whereas p16 mutations are never found in this lung cancer type but are prevalent in non-SCLC, a different type of lung cancer167.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Conclusions and discussion
What the sources say
- Not checked yetcites [167] Kaye, F. J. RB and cyclin dependent kinase pathways: defining a distinction between RB and p16 loss in lung cancer. Oncogene 21, 6908–6914 (2002). source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A similar increase in E2F3 activity in metastatic tumour cells could be indirectly related to the capacity of these cells to be more motile.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer progression > Loss of RB function is associated with increased metastatic potential.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Loss of RB has been shown to produce inappropriate migration of neurons in the developing mouse cortex141, a phenotype that is dependent on E2F3 activity69.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer progression > Loss of RB function is associated with increased metastatic potential.
What the sources say
- Not checked yetcites [141] Ferguson, K. L. et al. A cell-autonomous requirement for the cell cycle regulatory protein, Rb, in neuronal migration. EMBO J. 24, 4381–4391 (2005). source
- Not checked yetcites [69] McClellan, K. A. et al. Unique requirement for Rb/E2F3 in neuronal migration: evidence for cell cycle-independent functions. Mol. Cell. Biol. 27, 4825–4843 (2007). References 68 and 69 describe a novel function of RB in controlling cell migration, distinct from its role in the cell cycle, and show that E2F transcription factors might mediate this novel function of RB in vivo. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The cellular response to the presence or absence of RB might depend on complex regulatory networks that are poorly understood146.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Conclusions and discussion
What the sources say
- Not checked yetcites [146] Calzone, L., Gelay, A., Zinovyev, A., Radvanyl, F. & Barillot, E. A comprehensive modular map of molecular interactions in RB/E2F pathway. Mol. Syst. Biol. 4, 173 (2008). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Some of these functions seem difficult to reconcile with others: RB promotes terminal differentiation and cell cycle arrest in progenitor cells undergoing maturation, but it is also important for maintaining reversible cell cycle arrest in quiescent stem cells that must not permanently withdraw from the cell cycle and differentiate.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Conclusions and discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“But, loss of RB might also increase apoptotic and autophagic cell death and the ability to repair DNA lesions81,84, which might not be beneficial to tumour cells.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Conclusions and discussion
What the sources say
- Not checked yetcites [81] Bosco, E. E. & Knudsen, E. S. Differential role of RB in response to UV and IR damage. Nucleic Acids Res. 33, 1581–1592 (2005). source
- Not checked yetcites [84] Bosco, E. E. et al. RB signaling prevents replication-dependent DNA double-strand breaks following genotoxic insult. Nucleic Acids Res. 32, 25–34 (2004). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The Van Dyke group has published a series of elegant studies in mice expressing a truncated form of the SV40 large T oncoprotein, T121, which is thought to specifically inactivate the three Rb family members87,154–160.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Conclusions and discussion
What the sources say
- Not checked yetcites [87] Symonds, H. et al. p53-dependent apoptosis suppresses tumor growth and progression in vivo. Cell 78, 703–711 (1994). source
- Not checked yetcites [154] Yin, C., Knudson, C. M., Korsmeyer, S. J. & Van Dyke, T. Bax suppresses tumorigenesis and stimulates apoptosis in vivo. Nature 385, 637–640 (1997). source
- Not checked yetcites [155] Pan, H. et al. Key roles for E2F1 in signaling p53-dependent apoptosis and in cell division within developing tumors. Mol. Cell 2, 283–292 (1998). source
- Not checked yetcites [156] Lu, X. et al. Selective inactivation of p53 facilitates mouse epithelial tumor progression without chromosomal instability. Mol. Cell. Biol. 21, 6017–6030 (2001). source
- Not checked yetcites [157] Xiao, A., Wu, H., Pandolfi, P. P., Louis, D. N. & Van Dyke, T. Astrocyte inactivation of the pRb pathway predisposes mice to malignant astrocytoma development that is accelerated by PTEN mutation. Cancer Cell 1, 157–168 (2002). source
- Not checked yetcites [158] Simin, K. et al. pRb inactivation in mammary cells reveals common mechanisms for tumor initiation and progression in divergent epithelia. PLoS Biol. 2, E22 (2004). source
- Not checked yetcites [159] Hill, R., Song, Y., Cardiff, R. D. & Van Dyke, T. Selective evolution of stromal mesenchyme with p53 loss in response to epithelial tumorigenesis. Cell 123, 1001–1011 (2005). source
- Not checked yetcites [160] Hill, R., Song, Y., Cardiff, R. D. & Van Dyke, T. Heterogeneous tumor evolution initiated by loss of pRb function in a preclinical prostate cancer model. Cancer Res. 65, 10243–10254 (2005). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Cellular senescence suppresses tumours in vivo in response to oncogenic stress.
“Cellular senescence acts to suppress tumours in vivo in response to oncogenic stress”
The paper relies on this without support.
Loss of Rb is sufficient to initiate tumorigenesis in the pituitary, thyroid and adrenal glands.
“Furthermore, it is striking that the mechanisms of cancer initiation in the pituitary, thyroid and adrenal glands, in which loss of Rb is sufficient for tumorigenesis, are still largely unknown.”
The paper relies on this without support.
p107 and p130 are rarely mutated in human cancers and resemble RB in many respects.
“In particular, comparing the structure of RB with those of p107 and p130, which are rarely mutated in human cancers and yet are similar to RB in many ways, might help to identify mutant forms of RB that can distinguish specific cellular functions of RB.”
The paper relies on this without support.
High levels of cyclin–Cdk complexes may not fully phosphorylate and inactivate RB.
“In addition, even high levels of cyclin–Cdk complexes might be insufficient to fully phosphorylate — and functionally inactivate — RB.”
The paper relies on this without support.
Tumours acquire mutations that enhance endothelial cell recruitment and new blood vessel formation to overcome hypoxia.
“In order to over-come the growth-limiting effects of hypoxia, tumours select for mutations that increase their ability to recruit endothelial cells to form novel blood vessels in a process termed angiogenesis.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Continuous Cdk-mediated inactivation of pRb family proteins is a prerequisite for cell cycle progression, because active (hypo-phosphorylated) pocket-proteins drive cell cycle exit by sequestering E2F family transcription factors and repressing the genes required for DNA replication and cell division.3”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [3]
In the citing paper
“Loss-of-function mutations in the retinoblastoma gene product (RB) or its signaling network are considered requisite for cancer development”
From Dissecting the Unique Role of the Retinoblastoma Tumor Suppressor during Cellular Senescence (2010) · cites this paper as Burkhart and Sage, 2008
In the citing paper
“somatic mutations affecting p107 or p130 are rare in human cancers (Burkhart and Sage, 2008)”
From Dissecting the Unique Role of the Retinoblastoma Tumor Suppressor during Cellular Senescence (2010) · cites this paper as Burkhart and Sage, 2008
In the citing paper
“The importance of RB as a tumor suppressor gene is evident by the frequency of inactivating mutations that target RB or its pathway in human cancer; indeed, the RB pathway is thought to be disabled in virtually all tumor cells (Burkhart and Sage, 2008).”
From Dissecting the Unique Role of the Retinoblastoma Tumor Suppressor during Cellular Senescence (2010) · cites this paper as Burkhart and Sage, 2008
In the citing paper
“Together, these results implied that the role of CDK4/6 was to phosphorylate RB, priming it for inactivation by other CDKs later in G1, and releasing E2F transcription factors from RB constraint to allow their coordinate induction of a suite of genes whose activities are jointly required for initiation of S phase [reviewed in detail in (16) (29-31)].”
From Targeting CDK4 and CDK6: From Discovery to Therapy (2016) · cites this paper as [16]
In the citing paper
“Unlike CDKs 1 and 2 that phosphorylate many hundreds of cellular protein substrates (13), CDK4 is a surprisingly fastidious enzyme that has a restricted propensity to phosphorylate the retinoblastoma protein (RB1, hereafter RB) and two other RB-family proteins [RB2 (p130), RBL1 (p107)] (11, 14-16), but very few other substrates (17).”
From Targeting CDK4 and CDK6: From Discovery to Therapy (2016) · cites this paper as [16]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > Loss of RB function and cancer progression > Loss of RB function is associated with increased metastatic potential.
“correlative analyses have suggested that changes in RB expression are significantly associated with invasion and metastasis of oesophageal cancers99.”
§ Cellular mechanisms of tumour suppression by the retinoblastoma gene > References
“99. Sanseverino F pRb2/p130 and VEGF expression in endometrial carcinoma in relation to angiogenesis and histopathologic tumor grade.”
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Metadata
- Authors
- Burkhart, D. L., & Sage, J.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Sage, Julien
- Venue
- Nature Reviews Cancer
- Published
- 2008-07-24
- Volume
- 8
- Issue
- 9
- Pages
- 671-682
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC6996492
- OpenAlex
- W2071333117
- Cited by
- 974
- References
- 221
- Citations by year
- 2026: 20 · 2025: 45 · 2024: 32 · 2023: 47 · 2022: 54 · 2021: 75 · 2020: 61 · 2019: 48 · 2018: 49 · 2017: 58 · 2016: 53 · 2015: 57 · 2014: 66 · 2013: 73 · 2012: 90
- FWCI
- 4.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA114102)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Health Sciences › Medicine › Ophthalmology › Ocular Oncology and Treatments
- Keywords
- retinoblastoma gene, retinoblastoma protein, tumor suppression, tumor suppressor, tumor initiation, tumor progression, Rb inactivation, childhood cancer, mouse tumor model
- MeSH terms
- Animals, Cell Cycle, Cell Differentiation, Humans, Mutation, Neoplasm Invasiveness, Neoplasms, Neovascularization, Pathologic, Protein Binding, RNA Processing, Post-Transcriptional, Stem Cells, Genes, Tumor Suppressor, Genes, Retinoblastoma
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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