Platelet derived growth factor induces C- fos and C- myc mRNA in rat aortic smooth muscle cells in primary culture without elevation of intracellular Ca 2+ concentration

Abstract

Platelet derived growth factor (PDGF) has been shown to induce c- fos and c- myc protooncogenes. In the present study, we investigated the effects of genistein, a tyrosine kinase inhibitor, and NiCl 2, a Ca 2+ influx blocker, on PDGF-induced Ca 2+ transient and on expression of c- fos and c- myc mRNA. In the presence of extracellular Ca 2+, PDGF induced elevation of intracellular Ca 2+ concentration ([Ca 2+] i) and increases in c- fos and c- myc mRNA, as detected by reverse transcription polymerase chain reaction (RT PCR) and Northern hybridization. PDGF-induced [Ca 2+] i elevation was composed of an initial transient increase(first component) followed by steady state elevation (second component). Genistein (10,μ M) blocked the 1st, but not the 2nd, component of [Ca 2+] i elevation induced by PDGF. NiCl 2 (1mM) and removal of extracellular Ca 2+ inhibited the 2nd, but not the 1st, component. In the presence of 10 μM genistein and 1 mM NiCl 2, PDGF induced c- fos and c- myc mRNA, although the [Ca 2+] i elevation could be completely blocked by these two agents. These results indicate that elevation of [Ca 2+] i is not a prerequisite condition for PDGF to induce c- fos and/or c- myc mRNA in rat aortic smooth muscle cells in primary culture.