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 study, we provide evidence arguing against such a conclusion. Data obtained in five independent experiments showed that both c-fos RNA and protein expression were similar in 'young' and in senescent serum-stimulated WI-38 cells, suggesting that the previously reported suppression of c-fos induction is not an obligatory event in the process of cellular senescence. Likewise, expression of fra-1, c-jun and junB continued to be high in serum-stimulated senescent cells, while induction of fosB was reduced approximately fivefold. Among all genes tested fosB thus 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 exposed to serum exhibited normal AP-1-binding activity. These observations support the conclusion that a down-modulation of AP-1 is not crucial for human fibroblasts to enter the senescent state.