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 ar e increased by glucocorticoids and glucagon, and are decreased by insu lin; these effects seem to reflect changes in hepatic IGFBP-1 expressi on. Human HEP G2 hepatoma cells respond to cAMP or insulin with stimul ation or inhibition of IGFBP-1 expression, respectively; however, dexa methasone alone does not stimulate IGFBP-1 expression. Studies present ed here show that in the presence of cAMP and theophylline, nontransfe cted HEP G2 cells respond to further addition of dexamethasone with a approximately 70% rise in IGFBP-1 mRNA levels, and HEP G2 cells transf ected 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 stim ulatory effect of dexamethasone and cAMP, confered to the IGFBP-1 prom oter between 357 and 103 base pairs 5' to the mRNA cap site, is inhibi ted by insulin. Thus, the cis elements necessary to confer multihormon al regulation of IGFBP-1 expression appear to reside in a short stretc h of DNA just upstream from the IGFBP-1 transcription start site.