Dexamethasone stimulates expression of insulin-like growth factor binding protein-1 in HEP G2 human hepatoma cells.
Insulin-like growth factor binding protein-1 (IGFBP-1) serum levels are increased by glucocorticoids and glucagon, and are decreased by insulin; these effects seem to reflect changes in hepatic IGFBP-1 expression. Human HEP G2 hepatoma cells respond to cAMP or insulin with stimulation or inhibition of IGFBP-1 expression, respectively; however, dexamethasone alone does not stimulate IGFBP-1 expression. Studies presented here show that in the presence of cAMP and theophylline, nontransfected HEP G2 cells respond to further addition of dexamethasone with a approximately 70% rise in IGFBP-1 mRNA levels, and HEP G2 cells transfected with IGFBP-1 promoter constructs respond to further addition of dexamethasone with a approximately 70% rise in IGFBP-1 protein levels and a approximately 9-fold rise in IGFBP-1 promoter activity. The stimulatory effect of dexamethasone and cAMP, conferred to the IGFBP-1 promoter between 357 and 103 base pairs 5' to the mRNA cap site, is inhibited by insulin. Thus, the cis elements necessary to confer multihormonal regulation of IGFBP-1 expression appear to reside in a short stretch of DNA just upstream from the IGFBP-1 transcription start site.
Powell
D
D
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
Lee
P D
PD
DePaolis
L A
LA
Morris
S L
SL
Suwanichkul
A
A
D000818:Animals; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D000242:Cyclic AMP / Q000494:pharmacology; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D018970:Insulin-Like Growth Factor Binding Protein 1; D011401:Promoter Regions, Genetic; D011863:Radioimmunoassay; D013002:Somatomedins; D013268:Stimulation, Chemical; D013806:Theophylline / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D013002:Somatomedins; D003907:Dexamethasone; D013806:Theophylline; D000242:Cyclic AMP