Expression of c-fos and AP-1 activity in senescent human fibroblasts is not sufficient for DNA synthesis

doi:10.1083/jcb.119.6.1405

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Expression of c-fos and AP-1 activity in senescent human fibroblasts is not sufficient for DNA synthesis

DW Rose, G McCabe, JR Feramisco and M Adler
Department of Medicine, University of California, San Diego, La Jolla, CA 92093.

Human fibroblasts have a limited replicative life span when maintained in culture after which they become unresponsive to treatment with mitogens, a phenomenon most commonly called senescence. Experiments indicating that serum does not induce expression of the c-fos proto- oncogene in senescent fibroblasts raised the issue of a potential central role for c-fos in the phenotype of sustained growth arrest. This was directly tested by microinjection of oncogenic c-Ha-ras protein into senescent fibroblasts. While ras injection was found to induce marked nuclear c-fos expression and functional AP-1 transcription activity, this did not lead to DNA synthesis. These results suggest that the senescence phenotype cannot be solely attributed to the absence of c-fos expression and that the proliferative block in these cells is either independent of AP-1 transcriptional activity, downstream of it, or involves multiple molecular mechanisms.
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