Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer
Open accessAbstract
The murine Pten prostate cancer model described in this study recapitulates the disease progression seen in humans: initiation of prostate cancer with prostatic intraepithelial neoplasia (PIN), followed by progression to invasive adenocarcinoma, and subsequent metastasis with defined kinetics. Furthermore, while Pten null prostate cancers regress after androgen ablation, they are capable of proliferating in the absence of androgen. Global assessment of molecular changes caused by homozygous Pten deletion identified key genes known to be relevant to human prostate cancer, including those "signature" genes associated with human cancer metastasis. This murine prostate cancer model provides a unique tool for both exploring the molecular mechanism underlying prostate cancer and for development of new targeted therapies.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
p63 and PTEN are tumor suppressors that play a key role in breast and prostate tissue development.
“we inhibited p63 and PTEN expression, two genes that are described as tumor-suppressors that play a key role in breast and prostate tissue development (32–35).”
From Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens (2018) · cites this paper as [33]
The Introduction (page not specified) calls PTEN a tumor suppressor and links PTEN loss to mammary tumors and prostate cancer. The Results (page not specified) show that deleting Pten causes prostate tumors. Our copy does not address p63 or establish that either gene plays a key role in normal breast and prostate tissue development. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients
Bubendorf, L., Schöpfer, A., Wagner, U., Sauter, G., Moch, H., Willi, N., Gasser, T. C., & Mihatsch, M. J. (2000) · Human Pathology · doi:10.1053/hp.2000.6698 · Cited by 1,895 · see citing works
A history of prostate cancer treatment.
Denmeade, S. R., & Isaacs, J. T. (2002) · Nature reviews. Cancer · doi:10.1038/nrc801 · Cited by 591 · see citing works
Flagged first, then by citations
Research works printed but not linked: 6
- [1]1. Aaltomaa, S. ∙ Eskelinen, M. ∙ Lipponen, P. Expression of cyclin A and D proteins in prostate cancer and their relation to clinopathological variables and patient survival Prostate. 1999; 38:175-182 Crossref Scopus (71) PubMed Google Scholar
- [2]2. Abdulkadir, S.A. ∙ Magee, J.A. ∙ Peters, T.J. ... Conditional loss of Nkx3.1 in adult mice induces prostatic intraepithelial neoplasia Mol. Cell. Biol. 2002; 22:1495-1503 Crossref Scopus (196) PubMed Google Scholar
- [3]3. Backman, S. ∙ Stambolic, V. ∙ Mak, T. PTEN function in mammalian cell size regulation Curr. Opin. Neurobiol. 2002; 12:516-522 Crossref Scopus (77) PubMed Google Scholar
- [4]4. Bhatia-Gaur, R. ∙ Donjacour, A.A. ∙ Sciavolino, P.J. ... Roles for Nkx3.1 in prostate development and cancer Genes Dev. 1999; 13:966-977 Crossref Scopus (545) PubMed Google Scholar
- [5]5. Bose, S. ∙ Crane, A. ∙ Hibshoosh, H. ... Reduced expression of PTEN correlates with breast cancer progression Hum. Pathol. 2002; 33:405-409 Full Text Full Text (PDF) Scopus (125) PubMed Google Scholar
- [6]6. Bowen, C. ∙ Bubendorf, L. ∙ Voeller, H.J. ... Loss of NKX3.1 expression in human prostate cancers correlates with tumor progression Cancer Res. 2000; 60:6111-6115 PubMed Google Scholar
Cited by
Sorted by citations
Targeting PI3K signalling in cancer: opportunities, challenges and limitations
Engelman, J. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2664 · Cited by 2,445 · see citing works
Molecular determinants of resistance to antiandrogen therapy
Chen, C. D., Welsbie, D. S., Tran, C., Baek, S. H., Chen, R., Vessella, R., Rosenfeld, M. G., & Sawyers, C. L. (2004) · Nature Medicine · doi:10.1038/nm972 · Cited by 2,278 · see citing works
The translational landscape of mTOR signalling steers cancer initiation and metastasis
Hsieh, A. C., Liu, Y., Edlind, M. P., Ingolia, N. T., Janes, M. R., Sher, A., Shi, E. Y., Stumpf, C. R., Christensen, C., Bonham, M. J., et al. (2012) · Nature · doi:10.1038/nature10912 · Cited by 1,313 · see citing works
Self-citationFoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis
Paik, J.-H., Kollipara, R., Chu, G., Ji, H., Xiao, Y., Ding, Z., Miao, L., Tothova, Z., Horner, J. W., Carrasco, D. R., et al. (2007) · Cell · doi:10.1016/j.cell.2006.12.029 · Cited by 1,032 · see citing works
Essential role for nuclear PTEN in maintaining chromosomal integrity
Shen, W. H., Balajee, A. S., Wang, J., Wu, H., Eng, C., Pandolfi, P. P., & Yin, Y. (2007) · Cell · doi:10.1016/j.cell.2006.11.042 · Cited by 979 · see citing works
Self-citationPlaisier, S. B., Taschereau, R., Wong, J. A., & Graeber, T. G. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq636 · Cited by 468 · see citing works
Tumours with PI3K activation are resistant to dietary restriction
Kalaany, N. Y., & Sabatini, D. M. (2009) · Nature · doi:10.1038/nature07782 · Cited by 468 · see citing works
Clusterin inhibits apoptosis by interacting with activated Bax
Zhang, H., Kim, J. K., Edwards, C. A., Xu, Z., Taichman, R., & Wang, C.-Y. (2005) · Nature Cell Biology · doi:10.1038/ncb1291 · Cited by 453 · see citing works
Stiles, B., Groszer, M., Wang, S., Jiao, J., & Wu, H. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.06.008 · Cited by 230 · see citing works
Self-citationMultipotent and unipotent progenitors contribute to prostate postnatal development
Ousset, M., Van Keymeulen, A., Bouvencourt, G., Sharma, N., Achouri, Y., Simons, B. D., & Blanpain, C. (2012) · Nature Cell Biology · doi:10.1038/ncb2600 · Cited by 221 · see citing works
Zong, Y., Xin, L., Goldstein, A. S., Lawson, D. A., Teitell, M. A., & Witte, O. N. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905931106 · Cited by 203 · see citing works
Blattner, M., Liu, D., Robinson, B. D., Huang, D., Poliakov, A., Gao, D., Nataraj, S., Deonarine, L. D., Augello, M. A., Sailer, V., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.02.004 · Cited by 204 · see citing works
Fraser, M. M., Bayazitov, I. T., Zakharenko, S. S., & Baker, S. J. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2007.10.048 · Cited by 202 · see citing works
Memarzadeh, S., Xin, L., Mulholland, D. J., Mansukhani, A., Wu, H., Teitell, M. A., & Witte, O. N. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.11.002 · Cited by 201 · see citing works
Self-citationApplications of metabolomics to study cancer metabolism
Kaushik, A. K., & DeBerardinis, R. J. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.04.009 · Cited by 179 · see citing works
Fu, Y., Wey, S., Wang, M., Ye, R., Liao, C.-P., Roy-Burman, P., & Lee, A. S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807691105 · Cited by 180 · see citing works
Gao, H., Ouyang, X., Banach-Petrosky, W. A., Gerald, W. L., Shen, M. M., & Abate-Shen, C. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606836103 · Cited by 141 · see citing works
Purification and direct transformation of epithelial progenitor cells from primary human prostate
Goldstein, A. S., Drake, J. M., Burnes, D. L., Finley, D. S., Zhang, H., Reiter, R. E., Huang, J., & Witte, O. N. (2011) · Nature Protocols · doi:10.1038/nprot.2011.317 · Cited by 107 · see citing works
“The introduction of mouse models of prostate cancer, such as those involving the prostate-specific deletion of phosphatase and tensin homolog ( Pten ), the overexpression of c-Myc , and the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, has allowed researchers to further understand the pathways leading…”
Cooperative interactions of PTEN deficiency and RAS activation in melanoma metastasis
Nogueira, C., Kim, K.-H., Sung, H., Paraiso, K. H. T., Dannenberg, J.-H., Bosenberg, M., Chin, L., & Kim, M. (2010) · Oncogene · doi:10.1038/onc.2010.349 · Cited by 108 · see citing works
Zhou, Z., Flesken-Nikitin, A., & Nikitin, A. Y. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0768 · Cited by 91 · see citing works
Liu, P., Li, S., Gan, L., Kao, T. P., & Huang, H. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-2038 · Cited by 67 · see citing works
Laperrousaz, B., Porte, S., Gerbaud, S., Härmä, V., Kermarrec, F., Hourtane, V., Bottausci, F., Gidrol, X., & Picollet-D’hahan, N. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky030 · Cited by 54 · see citing works
Yan, Y., An, J., Yang, Y., Wu, D., Bai, Y., Cao, W., Ma, L., Chen, J., Yu, Z., He, Y., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201708478 · Cited by 53 · see citing works
Self-citationEstrogen receptor alpha controls gene expression via translational offsetting
Lorent, J., Rebello, R. J., Hoef, V. V., Lawrence, M. G., Szkop, K. J., Kusnadi, E., Samreen, B., Balanathan, P., Scharmann, K., Takizawa, I., et al. (2018) · doi:10.1101/507574 · Cited by 46 · see citing works
Qin, T., Barron, L., Xia, L., Huang, H., Villarreal, M. M., Zwaagstra, J., Collins, C., Yang, J., Zwieb, C., Kodali, R., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.13343 · Cited by 40 · see citing works
- Authors
- Wang, S., Gao, J., Lei, Q., Rozengurt, N., Pritchard, C., Jiao, J., Thomas, G. V., Li, G., Roy-Burman, P., Nelson, P. S., Liu, X., & Wu, H.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of California, Los Angeles (US)
- Fred Hutch Cancer Center (US)
- Corresponding author
- Wu, Hong
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2003-09
- Volume
- 4
- Issue
- 3
- Pages
- 209-221
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2046234516
- Cited by
- 1,109
- References
- 2
- Citations by year
- 2026: 10 · 2025: 30 · 2024: 51 · 2023: 40 · 2022: 40 · 2021: 32 · 2020: 50 · 2019: 50 · 2018: 52 · 2017: 43 · 2016: 44 · 2015: 65 · 2014: 60 · 2013: 89 · 2012: 64
- FWCI
- 32.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk059125-02)
- National Cancer Institute (CA-98-013, CA 59705, R01CA059705)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK065204, DK65204, DK59125)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Diagnosis and Treatment
- Keywords
- PTEN, prostate cancer, tumor suppressor loss, metastasis, prostatic intraepithelial neoplasia, androgen deprivation therapy, targeted therapy
- MeSH terms
- Animals, Cell Division, Humans, Male, Neoplasm Metastasis, Phosphoric Monoester Hydrolases, Prostatic Hyperplasia, Prostatic Neoplasms, Proto-Oncogene Proteins, Protein Serine-Threonine Kinases, Gene Deletion, Mice, Knockout, Prostatic Intraepithelial Neoplasia, Gene Expression Profiling, Tumor Suppressor Proteins, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, Mice
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.
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 ›
Are you an author, or do you see a problem with this page? Request a review
