Expression of c-fos and AP-1 activity in senescent human fibroblasts is not sufficient for DNA synthesis.
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.
Rose
D W
DW
Department of Medicine, University of California, San Diego, La Jolla, CA 92093.
McCabe
G
G
Feramisco
J R
JR
Adler
M
M
D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D008845:Microinjections; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000187:drug effects; D016283:Proto-Oncogene Proteins p21(ras) / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000187:drug effects; D014157:Transcription Factors / Q000096:biosynthesis* / Q000187:drug effects; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000187:drug effects
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D001616:beta-Galactosidase; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)