Cyclic adenosine 3',5'-monophosphate inhibits insulin-like growth factor I gene expression in rat glioma cell lines: evidence for regulation of transcription and messenger ribonucleic acid stability.
cAMP inhibits growth and stimulates differentiation in glioma cells. We examined the effect of cAMP on insulin-like growth factor I (IGF-I) gene expression in the C6 cell line, a rat glioma cell line previously reported to grow in response to autocrine IGF-I. cAMP potently inhibited IGF-I messenger RNA (mRNA) and peptide secretion in C6 cells, associated with an attenuation of DNA synthesis. Exogenous IGF-I peptide at least partially prevented the inhibition of DNA synthesis, suggesting that the reduction in IGF-I biosynthesis may contribute to the inhibitory effect of cAMP on C6 cell growth. cAMP also inhibited IGF-I mRNA in rat RG2 glioma cells, but not in three other nonglioma tumor cell lines. The nuclear IGF-I pre-mRNA level and the half-life of mature IGF-I mRNA were both reduced by cAMP in C6 cells, suggesting effects on gene transcription and mRNA stability. However, cAMP had no effect on the activities of IGF-I exon 1 promoter-luciferase constructs. Protein synthesis inhibition partially reduced the inhibition of IGF-I mRNA by cAMP. Inhibition of cAMP-activated protein kinase A activity by H89 did not alter the inhibition of IGF-I gene expression in response to cAMP, suggesting that protein kinase A does not mediate the cAMP inhibitory effect on IGF-I gene expression.
Wang
L
L
Department of Biochemistry, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
Adamo
M L
ML
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D005910:Glioma / Q000235:genetics / Q000473:pathology; D006207:Half-Life; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012322:RNA Precursors / Q000037:antagonists & inhibitors; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D011500:Protein Synthesis Inhibitors; D012322:RNA Precursors; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D003513:Cycloheximide; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases