Contrasting ability of antiestrogens to inhibit MCF-7 growth stimulated by estradiol or epidermal growth factor.
A potential mechanism is described by which a growth factor may prevent the action of antiestrogens or reactive the growth of hormone-responsive breast carcinoma in patients undergoing tamoxifen (TAM) treatment. Epidermal growth factor (EGF)-stimulated growth (10(-8) M EGF) was assayed in the MCF-7 breast cancer cell line in the presence of various concentrations (10(-10) to 10(-6) M) of three antiestrogens, 4-hydroxytamoxifen (OH TAM), TAM and ICI 164384. In each case, the EGF-stimulated increases in DNA were not inhibited by the antiestrogen. OH TAM and ICI 164384 inhibited estradiol (E2) stimulated cell proliferation in a dose-related fashion. However, in the presence of both E2 and EGF, these two antiestrogens inhibited E2 effects only; EGF promotion of growth was unaffected. Pretreatment of MCF-7 cells for 2 days with either OH TAM or ICI 164384 did not inhibit EGF-induced increases in cell proliferation. We propose that eventual antiestrogen therapeutic failure may be caused by the paracrine influences of growth factors from neighboring cells.
Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
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Cormier
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Jordan
D001943:Breast Neoplasms / Q000188:drug therapy*; D002460:Cell Line; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D053284:Polyunsaturated Alkamides; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000627:therapeutic use; D013997:Time Factors
D004273:DNA, Neoplasm; D004965:Estrogen Antagonists; D053284:Polyunsaturated Alkamides; D013629:Tamoxifen; C038345:droloxifene; D004958:Estradiol; D004815:Epidermal Growth Factor; C051781:ICI 164384