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

Oncogene. 1999 Sep 2;18(35):4974-82. doi: 10.1038/sj.onc.1202880.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Cycle
  • Cell Division
  • Cell Line, Transformed
  • Cell Transformation, Neoplastic* / genetics
  • Cells, Cultured
  • Cellular Senescence*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / deficiency
  • Cyclins / genetics
  • Cyclins / physiology*
  • Doxorubicin / pharmacology
  • Fibroblasts / cytology*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Deletion
  • Gene Expression / drug effects
  • Mice
  • Mice, Knockout
  • Oncogene Protein p21(ras) / genetics
  • Oncogene Protein p21(ras) / metabolism*
  • Serial Passage
  • Transduction, Genetic
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism


  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Tumor Suppressor Protein p53
  • Doxorubicin
  • Oncogene Protein p21(ras)