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 RasV12 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 H2O2, 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.
|Original language||English (US)|
|Number of pages||8|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Apr 11 2003|
Bibliographical noteFunding Information:
We thank R.A. Weinberg for the pBabe-tert-, S. Lowe for the pBabe-lacZ, -puro, and -ras V12 constructs, G. Nolan for the Phoenix cells, and T. Thi-Bui for the technical assistance. Research was supported by grants from the American Cancer Society and the National Institute of Health.
- Cell cycle