Comparative studies on the effects of steroidal and nonsteroidal oestrogen antagonists on the proliferation of human breast cancer cells.
Pure and partial agonist antioestrogens, exemplified by ICI 164,384 and tamoxifen or 4-hydroxytamoxifen (4'-OHT) respectively, differ in their capacity to inhibit the growth of MCF-7 human breast cancer cells. Under basal conditions which maintain but do not permit proliferation of MCF-7 cells, growth rate was enhanced by oestradiol, Phenol Red, insulin and 4'-OHT but not by ICI 164,384. Oestradiol and insulin together enhanced cell growth rate synergistically. 4'-OHT, but not ICI 164,384, similarly increased insulin-stimulated cell growth in the absence of oestradiol. ICI 164,384 blocked the stimulatory action of 4'-OHT. The stimulatory effect of the peptide growth factors TGF-alpha and IGFI on MCF-7 cells were attenuated by ICI 164,384 and 4'-OHT; ICI 164,384 was more effective than 4'-OHT. The antiproliferative action of ICI 164,384 on oestradiol or growth factor stimulated MCF-7 cells was only weakly inhibited by TGF-beta antibodies.
Wakeling
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Bioscience Department, ICI Pharmaceuticals, Macclesfield, Cheshire, U.K.
D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D053284:Polyunsaturated Alkamides; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*
D004965:Estrogen Antagonists; D007328:Insulin; D053284:Polyunsaturated Alkamides; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol; C051781:ICI 164384