Dissociation between activation of growth-related genes and mitogenic responses of neonatal vascular smooth muscle cells

Robert H Weiss, Harlan E. Ives

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13 Citations (Scopus)

Abstract

In neonatal vascular smooth muscle (VSM) cells, activation of protein kinase C can block the mitogenic response to α-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 expresion was dissociated during PMA-mediated growth inhibition.

Original languageEnglish (US)
Pages (from-to)617-622
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume181
Issue number2
DOIs
StatePublished - Dec 16 1991

Fingerprint

Vascular Smooth Muscle
Thrombin
Smooth Muscle Myocytes
Muscle
Genes
Chemical activation
Cells
Acetates
Growth
Protein Kinase C
Messenger RNA
myc Genes
Cell growth
phorbol-12-myristate
Cell Cycle
Down-Regulation
DNA

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

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abstract = "In neonatal vascular smooth muscle (VSM) cells, activation of protein kinase C can block the mitogenic response to α-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 expresion was dissociated during PMA-mediated growth inhibition.",
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AU - Ives, Harlan E.

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N2 - In neonatal vascular smooth muscle (VSM) cells, activation of protein kinase C can block the mitogenic response to α-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 expresion was dissociated during PMA-mediated growth inhibition.

AB - In neonatal vascular smooth muscle (VSM) cells, activation of protein kinase C can block the mitogenic response to α-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 expresion was dissociated during PMA-mediated growth inhibition.

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