Dissociation between activation of growth-related genes and mitogenic responses of neonatal vascular smooth muscle cells.
In neonatal vascular smooth muscle (VSM) cells, activation of protein kinase C can block the mitogenic response to alpha-thrombin. The molecular mechanism for this growth inhibition was investigated by looking at early transcriptional events in the cell cycle. Both thrombin and phorbol-12-myristate-13-acetate (PMA) induced mRNA for the c-myc oncogene; peak levels of expression were found 4-5 h after exposure to either agent. When thrombin and PMA were added together, c-myc expression was increased synergistically; down-regulation of protein kinase C suppressed induction of c-myc by thrombin. Thus, c-myc expression varied inversely with cell growth under these conditions. Thrombin and PMA also both induced expression of mRNA for the PDGF-A chain over 4-7h. As for c-myc, PMA and thrombin synergistically increased expression of the PDGF A-chain under conditions where PMA inhibits thrombin-induced DNA synthesis. Thus, mitogenesis and early growth-related gene expression was dissociated during PMA-mediated growth inhibition.
Weiss
R H
RH
Division of Nephrology, University of California, San Francisco 94143.
Ives
H E
HE
D000818:Animals; D000831:Animals, Newborn; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc / Q000235:genetics; D007700:Kinetics; D008938:Mitosis / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011493:Protein Kinase C; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate