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Oncogene. 1999 Sep 2;18(35):4974-82.

Murine fibroblasts lacking p21 undergo senescence and are resistant to transformation by oncogenic Ras.

Author information

1
Department of Immunology and Oncology, Centro Nacional de Biotecnología, CSIC, Campus de Cantoblanco, Madrid E-28049, Spain.

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.

PMID:
10490832
DOI:
10.1038/sj.onc.1202880
[Indexed for MEDLINE]
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