Platelet derived growth factor induces c-fos and c-myc mRNA in rat aortic smooth muscle cells in primary culture without elevation of intracellular Ca2+ concentration.
Platelet derived growth factor (PDGF) has been shown to induce c-fos and c-myc proto-oncogenes. In the present study, we investigated the effects of genistein, a tyrosine kinase inhibitor, and NiCl2, a Ca2+ influx blocker, on PDGF-induced Ca2+ transient and on expression of c-fos and c-myc mRNA. In the presence of extracellular Ca2+, PDGF induced elevation of intracellular Ca2+ concentration ([Ca2+]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 [Ca2+]i elevation was composed of an initial transient increase (first component) followed by steady state elevation (second component). Genistein (10 microM) blocked the 1st, but not the 2nd, component of [Ca2+]i elevation induced by PDGF. NiCl2 (1 mM) and removal of extracellular Ca2+ inhibited the 2nd, but not the 1st, component. In the presence of 10 microM genistein and 1 mM NiCl2, PDGF induced c-fos and c-myc mRNA, although the [Ca2+]i elevation could be completely blocked by these two agents. These results indicate that elevation of [Ca2+]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.
Nishimura
J
J
Division of Molecular Cardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kobayashi
S
S
Shikasho
T
T
Kanaide
H
H
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D016762:Genes, fos / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009532:Nickel / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011519:Proto-Oncogenes / Q000187:drug effects*; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects*
D007529:Isoflavones; D010982:Platelet-Derived Growth Factor; D009532:Nickel; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D002118:Calcium