Bcl-2 promotes premature senescence induced by oncogenic Ras

Biochem Biophys Res Commun. 2003 Apr 11;303(3):800-7. doi: 10.1016/s0006-291x(03)00402-9.


The expression of the apoptosis inhibitory protein, Bcl-2, is increased in naturally senescing human fibroblasts and upon induction of their senescence-like growth arrest by oxidative stress, implying its role in maintaining their extended viability. Oncogenic Ras(V12) protein induces signaling cascades that result in the premature senescence of primary fibroblast cells, which are insensitive to oncogene-dependent apoptosis. Here we show that constitutive expression of Bcl-2 accelerates selected features of the Ras-induced senescence program in primary human fibroblasts. Yet, Bcl-2 also inhibits fibroblast apoptosis induced by exogenous H(2)O(2), while both signals induce an increased endogenous Bcl-2 expression in these cells. Together, these data suggest a context-dependent phenotypic function of Bcl-2 in the regulation of overlapping cell fate specification programs, with potential implications for both physiology and multistep tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / genetics
  • Apoptosis / physiology
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Line
  • Cell Transformation, Neoplastic
  • Cellular Senescence / genetics
  • Cellular Senescence / physiology*
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Genes, bcl-2
  • Humans
  • Oxidative Stress
  • Phenotype
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Signal Transduction
  • Transduction, Genetic
  • ras Proteins / physiology*


  • Proto-Oncogene Proteins c-bcl-2
  • ras Proteins