Stimulation and inhibition of growth by EGF in different A431 cell clones is accompanied by the rapid induction of c-fos and c-myc proto-oncogenes.

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Abstract
Stimulation of quiescent fibroblasts to growth by polypeptide growth factors is accompanied by the rapid induction of c‐fos and c‐myc proto‐oncogenes. In contrast to fibroblasts, A431 cells respond to epidermal growth factor (EGF) with a decreased growth rate. Here we report that, in spite of its growth inhibitory effect, EGF rapidly induces transient expression of c‐fos mRNA, followed by the synthesis of nuclear c‐fos protein. In addition, EGF treatment resulted in elevated levels of c‐myc expression. Practically identical results were obtained with variant A431 clones that are resistant to the inhibitory effect of EGF on cell proliferation. These observations suggest that in A431 cells c‐fos and c‐myc induction is a primary consequence of growth factor‐receptor interaction. Indeed, efficient induction of both genes was also observed with cyanide bromide‐cleaved EGF, which has previously been shown to be non‐mitogenic but able to trigger early events induced by EGF. We observed strong induction of c‐fos and to a lesser extent of c‐myc also by TPA, and by the calcium ionophore A23187, indicating an important role for kinase C in proto‐oncogene activation by growth factors.