Phorbol esters differentially regulate the expression of insulin-like growth factor-binding proteins in endometrial carcinoma cells.
We have examined the effects of protein kinase-C (PKC) activation on expression of the six known insulin-like growth factor-binding proteins (IGFBPs) by human endometrial carcinoma cells. Each of six known IGFBPs was expressed in one or more of the three cell lines examined. The addition of 10(-7) M 4 beta-phorbol 12-myristate 13-acetate (PMA) to HEC-50 and HEC-1B cells resulted in changes in cell morphology, growth inhibition, activation of PKC, and an increase in expression of IGFBP-1. PMA had no effect on these parameters in the Ishikawa cell line, which did not express IGFBP-1. In HEC-50 cells, the effect of PMA was blocked by the concomitant addition of the PKC inhibitor staurosporin and the simultaneous addition of cycloheximide. PMA also resulted in an increase in IGFBP-3 in HEC-50 cells and an increase in IGFBP-6 expression in HEC-1B cells. In contrast, IGFBP-3 expression was down-regulated by PMA in HEC-1B and Ishikawa cells. The abundance of IGFBP-2 and IGFBP-5 mRNAs was also reduced in HEC-1B and Ishikawa cells, respectively. IGFBP-4 was expressed only in HEC-50 cells and was not affected by PMA treatment. These data establish a role for the PKC pathway in regulation of expression of IGFBP-1, -2, -3, and -5 in endometrial adenocarcinoma cells and illustrate the complexity of cell type-specific expression of the IGFBPs.
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000470:Alkaloids / Q000494:pharmacology; D015152:Blotting, Northern; D000001:Calcimycin / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D007700:Kinetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019311:Staurosporine; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D019284:Thapsigargin; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D013729:Terpenes; D000001:Calcimycin; D019284:Thapsigargin; D003513:Cycloheximide; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate