AbstractProto‐oncogenes are cellular homologues of viral oncogenes that are known to be associated with regulation of growth and differentiation. The c‐myc and c‐fos proto‐oncogenes have been extensively studied by using established cell lines but to a lesser extent by using normal cells. Using physiologic growth modulators, we have shown that mitotic stimulation of normal human dermal fibroblasts is associated with induction of c‐myc and c‐fos, but that growth inhibition of these cells is not necessarily accompanied by their down‐regulation. When treated with both serum and interferon‐alpha during quiescence, fibroblasts were delayed in their progress into the S‐phase of the cell cycle as compared to cells treated with serum alone and displayed substantial growth inhibition as measured by cell number at the end of 1 week. However, this growth inhibition was not preceded by down‐regulation or delay in induction of c‐myc and c‐fos mRNA. The above studies suggest that in normal fibroblasts growth inhibition is not necessarily dependent on down‐regulation of transcription of either c‐myc or c‐fos and that interferon may act to inhibit cell growth either through a post‐transcriptional effect on cellular proto‐oncogenes necessary for cell proliferation or through induction of other, as yet unrecognized gene
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