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  • Original Paper
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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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Acknowledgements

We are grateful to Drs María A Blasco, Ignacio Palmero and Frank Bringold for their suggestions and for critically reading the manuscript. C Pantoja was supported by a fellowship from the Spanish Ministry of Education and Culture (MEC). Research at the laboratory of M Serrano is supported by the Spanish Council for Scientific Research (CSIC), by grants PM95-0014 (MEC) and 08.1/0043.2/98 (Regional Government of Madrid), and by a core grant from the Department of Immunology and Oncology (DIO). The DIO is funded by Pharmacia & Upjohn and the CSIC.

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Pantoja, C., Serrano, M. Murine fibroblasts lacking p21 undergo senescence and are resistant to transformation by oncogenic Ras. Oncogene 18, 4974–4982 (1999). https://doi.org/10.1038/sj.onc.1202880

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