SUPPRESSION OF THE GROWTH FACTOR-MEDIATED INDUCTION OF C-FOS AND DOWN-MODULATION OF AP-1-BINDING ACTIVITY ARE NOT REQUIRED FOR CELLULAR SENESCENCE

It has been suggested that the impaired response of the c-fos gene to serum growth factors and the concomitant loss of AP-1 activity may be a crucial step in the process of cellular senescence. In the present s tudy, we provide evidence arguing against such a conclusion. Data obta ined in five independent experiments showed that both c-fos RNA and pr otein expression were similar in 'young' and in senescent serum-stimul ated WI-38 cells, suggesting that the previously reported suppression of c-fos induction is not an obligatory event in the process of cellul ar senescence. Likewise, expression of fra-1, c-jun and junB continued to be high in serum-stimulated senescent cells, while induction of fo sB was reduced approximately fivefold. Among all genes tested fosB thu s seems to be the most suitable marker for the detection of senescent cells. Stimulated senescent cells showed only a approximately twofold reduction of AP-1-binding activity, and senescent cells continuously e xposed to serum exhibited normal AP-1-binding activity. These observat ions support the conclusion that a down-modulation of AP-1 is not cruc ial for human fibroblasts to enter the senescent state.