Multihormonal regulation of insulin-like growth factor-I-related protein in MCF-7 human breast cancer cells.
MCF-7 human breast cancer cells have been studied for hormonal regulation of secretion of an insulin growth factor-I (IGF-I)-related growth factor. 17 beta-Estradiol, which is required for tumorigenesis of the cell line in the nude mouse and which stimulates proliferation in vitro, was able to significantly induce IGF-I secretion at 10(-13) M, with maximal induction at 10(-11) M. Under optimal conditions IGF-I could be induced 4-fold after 4 days. Demonstration of estrogenic stimulations required removal of phenol red, a weak estrogen, from the cell culture medium. In addition to estrogen, insulin, epidermal growth factor, and transforming growth factor alpha induce both cellular proliferation and IGF-I secretion, while growth inhibitory antiestrogens, transforming growth factor beta, and glucocorticoids have the opposite effect. In each case, modulations in IGF-I secretion preceeded effects on cellular proliferation. IGF-I was not regulated by human GH, basic fibroblast growth factor, platelet-derived growth factor, or PRL, none of which affected proliferation rate. Thus, regulation of IGF-I secretion in human breast cancer is controlled by different hormones from those previously reported in human fibroblasts. Regulation of IGF-I by neither estrogen nor antiestrogen was associated with changes in steady-state mRNA levels; thus regulation may occur at a step beyond mRNA. We conclude that IGF-I production is tightly coupled to growth regulation by estrogens, antiestrogens, and other hormones and may contribute to autocrine and/or paracrine growth regulation by these agents in breast cancer.
D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D006728:Hormones / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D013002:Somatomedins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D006133:Growth Substances; D006728:Hormones; D007328:Insulin; D010636:Phenols; D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I