title: 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.
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.
authors.forename: R
authors.initials: R
authors.lastname: Bravo
authors.forename: J
authors.initials: J
authors.lastname: Burckhardt
authors.forename: T
authors.initials: T
authors.lastname: Curran
authors.forename: R
authors.initials: R
authors.lastname: Müller
mesh_terms: D000001:Calcimycin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D009857:Oncogenes; D014176:Protein Biosynthesis; D011493:Protein Kinase C; D011494:Protein Kinases / Q000502:physiology; D000090063:Proto-Oncogene Mas; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D000001:Calcimycin; D004815:Epidermal Growth Factor; D011494:Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate