The DOI matches its Crossref record; 77 of the 78 references it cites were found in a registry or an index.
Murine fibroblasts lacking p21 undergo senescence and are resistant to transformation by oncogenic Ras.
Abstract
The cell-cycle inhibitor p21 is upregulated during senescence and upon induction of senescence-like arrest by oncogenic Ras. We have used primary fibroblasts derived from p21-null mice to evaluate the role of p21 in these processes. We find that primary p21-/- cells enter senescence and have a lifespan similar to wild-type cells. Upon immortalization, most wild-type and p21-/- cultures acquire alterations in either p53 or p16INK4a, further indicating that p21-deficiency is not sufficient by itself to allow immortalization. Primary p21-/- cells, like wild-type cells, respond to oncogenic Ras by accumulating p53 and p16INK4a, and by decreasing their proliferation rate. In agreement with this, p21-/- cells are refractory to neoplasic transformation by oncogenic Ras when compared to p53-/- cells. We conclude that, in murine fibroblasts, p21 is not essential neither for senescence nor for preventing neoplasic transformation by oncogenic Ras.
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“Increased expression of p21 also plays a role in induction of senescence, particularly during its initiation.26”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [26]
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Cites
WAF1, a potential mediator of p53 tumor suppression
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The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.
Wade Harper, J. (1993) · Cell · doi:10.1016/0092-8674(93)90499-g · Cited by 5,651
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
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“Accordingly, rodent cells de®cient in p53 or p16 are e ciently transformed by oncogenic Ras (Serrano et al., 1997; Lloyd et al., 1997; Zhu et al., 1998; Lin et al., 1998).”
BackgroundMethodResultInfluentialExtension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
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p21 is a universal inhibitor of cyclin kinases
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Inhibitors of mammalian G1 cyclin-dependent kinases.Preprint
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Production of high-titer helper-free retroviruses by transient transfection.
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Mice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
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The RB and p53 pathways in cancer
Sherr, C. J., & McCormick, F. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00102-2 · Cited by 1,690
“However, cells lacking Cip1 are not immortal and undergo efficient p19Arf-induced arrest (Pantoja and Serrano, 1999; Modestou et al. 2001).”
BackgroundForging a signature of in vivo senescence
Sharpless, N. E., & Sherr, C. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3960 · Cited by 1,104
The signals and pathways activating cellular senescence
Ben-Porath, I., & Weinberg, R. A. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.10.013 · Cited by 1,046
The INK4a/ARF network in tumour suppression
Sherr, C. J. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35096061 · Cited by 1,001
Tuveson, D. A., Shaw, A. T., Willis, N. A., Silver, D. P., Jackson, E. L., Chang, S., Mercer, K. L., Grochow, R., Hock, H., Crowley, D., et al. (2004) · Cancer Cell · doi:10.1016/s1535-6108(04)00085-6 · Cited by 798
Metadata
- Authors
- Pantoja, C., & Serrano, M.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Venue
- Oncogene
- Published
- 1999-09-02
- Volume
- 18
- Issue
- 35
- Pages
- 4974-4982
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2081779271
- Cited by
- 201
- References
- 78
- Citations by year
- 2025: 3 · 2023: 6 · 2022: 4 · 2021: 1 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 6 · 2015: 7 · 2014: 7 · 2013: 11 · 2012: 6
- FWCI
- 8.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- p21, cellular senescence, oncogenic Ras, oncogenic transformation, p53, p16INK4a, cell cycle inhibitors, fibroblasts, cell immortalization
- MeSH terms
- Animals, Cell Cycle, Cell Division, Cell Line, Transformed, Cell Transformation, Neoplastic, Cells, Cultured, Doxorubicin, Fibroblasts, Serial Passage, Transduction, Genetic, Oncogene Protein p21(ras), Gene Expression, Tumor Suppressor Protein p53, Cyclins, 3T3 Cells, Cellular Senescence, Gene Deletion, Mice, Knockout, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p21, Mice
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