P21 v- <i>ras</i> Inhibits Induction of c- <i>myc</i> and c- <i>fos</i> Expression by Platelet-Derived Growth Factor

Abstract

The viral oncogene v-ras inhibited the platelet-derived growth factor (PDGF)-induced upregulation of c-myc and c-fos proto-oncogene expression in fibroblast monolayers. These v-ras-containing cells proliferated in the absence of c-myc induction and no longer required PDGF to support growth. Fibroblasts expressing v-ras continued to express the same number of functional PDGF receptors on their surface as uninfected cells, yet the usual induction of transcription of the genes c-myc, c-fos, and JE in response to PDGF stimulation did not occur in the presence of newly introduced v-ras or chronic v-ras gene expression, and synthesis of c-myc protein did not occur. This inhibitory effect on growth factor-mediated induction of cellular proto-oncogenes was specific for PDGF in that induction of the c-myc and c-fos genes by certain other factors was not impaired.