Insulin-like growth factor-I and its autocrine role in growth of MCF-7 human breast cancer cells in culture.
Human MCF-7 breast cancer cells have been studied to determine their suitability as an autocrine model for the synthesis, secretion and action of insulin-like growth factor-I (IGF-I). Secretion of immunoreactive (ir-) IGF-I into serum-free medium was very low (less than 500 pg/10(6) cells per day). Northern blot hybridization detected at least two IGF-I messenger RNA transcripts (approximately 4.6 and approximately 1.8 kb) which were similar in size to those reported in other human and rat tissues. IGF-II mRNA was also detected but at low abundance. Cell proliferation was stimulated in a dose-responsive manner by exogenous IGF-I (10-30 ng/ml). Addition of a monoclonal antibody against IGF-I to MCF-7 cells in serum-free medium caused an inhibition of cell proliferation, suggesting that endogenous locally produced IGF-I does play an autocrine/paracrine role in MCF-7 cell growth. Proliferation of MCF-7 cells was sensitive to oestradiol (10 nM) in the absence but not in the presence of the weakly oestrogenic pH indicator phenol red. Neither IGF-I secretion nor IGF-I mRNA synthesis, however, was affected by addition of oestradiol. Similarly, GH, dexamethasone or dexamethasone plus oestradiol had no effect on either parameter. These data indicate that MCF-7 cells synthesize, secrete and respond to IGF-I. The very low levels of ir-IGF-I produced and their apparent lack of hormonal modulation suggest, however, that further studies are required to establish whether IGF-I plays a major physiological role in growth and development of MCF-7 cells.
Freed
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Medical Research Centre, Prince Henry's Hospital Campus, Monash Medical Centre, Melbourne, Victoria, Australia.
Herington
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D000818:Animals; D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008954:Models, Biological; D010637:Phenolsulfonphthalein / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013002:Somatomedins / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D013002:Somatomedins; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D003907:Dexamethasone; D013006:Growth Hormone; D010637:Phenolsulfonphthalein