Murine fibroblasts lacking p21 undergo senescence and are resistant to transformation by oncogenic Ras.
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.
Pantoja
C
C
Department of Immunology and Oncology, Centro Nacional de Biotecnología, CSIC, Campus de Cantoblanco, Madrid E-28049, Spain.
Serrano
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M
D016475:3T3 Cells; D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002478:Cells, Cultured; D016922:Cellular Senescence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004317:Doxorubicin / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism*; D012692:Serial Passage; D014161:Transduction, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C493957:Cdkn1a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D015689:Oncogene Protein p21(ras)