Rapid regulation of albumin transcription by insulin and phorbol esters in rat hepatoma cells.
The short-term effects of insulin and phorbol esters on the regulation of the albumin gene in rat H4IIE (H4) hepatoma cells were investigated and compared to the expression of a gene known to be inhibited by these agents, phosphoenol pyruvate carboxykinase (PEPCK). Both insulin and phorbol esters inhibited transcription of the albumin gene in a rapid, dose-dependent manner. Within 15 min, albumin transcription was reduced by approx. 80%. The inhibitory effects of insulin were evident at concentrations of insulin as low as 5.10(-11)M, suggesting that these effects were mediated through insulin-specific pathways. The ability of both phorbol esters and insulin to inhibit albumin transcription suggests that the negative control of this gene is a stable feature in H4 cells. The effect of phorbol esters to mimic insulin action on the albumin gene, and on several other genes in this cell line, implies that a common pathway may be shared by both insulin and phorbol esters.
Messina
J L
JL
Department of Physiology, SUNY Health Science Center, Syracuse 13210.
D000418:Albumins / Q000235:genetics* / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007328:Insulin / Q000502:physiology*; D007700:Kinetics; D008114:Liver Neoplasms, Experimental; D009281:Naphthalenes; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics / Q000378:metabolism; D011083:Polycyclic Compounds / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000418:Albumins; D000470:Alkaloids; D007328:Insulin; D009281:Naphthalenes; D011083:Polycyclic Compounds; D003513:Cycloheximide; D011493:Protein Kinase C; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D019311:Staurosporine; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate