Coordinated effects of insulin-like growth factor I on inhibitory pathways of cell cycle progression in cultured cardiac muscle cells.
Insulin-like growth factor I (IGF I) plays a key role in the regulation of cell proliferation. Progression of the cell cycle is regulated by stimulatory and inhibitory pathways. In order to understand the mechanisms through which IGF I regulates cardiac muscle growth, we have studied the effects of IGF I on inhibitory pathways involving p53 and WAF1 in cultured cardiac muscle cell line H9C2. The onset of DNA synthesis in response to IGF I stimulation was preceded by activation of p53 expression. In addition, IGF I increased p53-dependent and p53-independent induction of WAF1 in H9C2 cells. Dose-response studies showed that IGF I effects on p53-dependent and p53-independent induction of WAF1 occur at physiological concentrations of IGF I. These data indicate that IGF I coordinately regulates inhibitory pathways of cell cycle progression, and that p53-dependent and p53-independent induction of WAF1 may provide negative control mechanisms to regulate stimulatory pathways of cell cycle progression activated by IGF I.
Chen
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WH
Department of Medicine, University of California, Irvine, 92717, USA.
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Wang
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D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D004622:Embryo, Mammalian; D015870:Gene Expression; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008156:Luciferases / Q000235:genetics; D009206:Myocardium / Q000166:cytology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology
C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D007334:Insulin-Like Growth Factor I; D004247:DNA; D008156:Luciferases