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.