Contrasting ability of antiestrogens to inhibit MCF-7 growth stimulated by estradiol or epidermal growth factor

• Published in: European journal of cancer & clinical oncology Vol. 25; no. 1; pp. 57 - 63
• Main Authors: Cormier, Ethel M., Craig Jordan, V.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 1989; New York, NY Pergamon Press
• Subjects: Antineoplastic agents; Biological and medical sciences; Breast Neoplasms - drug therapy; Cell Line; DNA, Neoplasm - biosynthesis; Dose-Response Relationship, Drug; Epidermal Growth Factor - pharmacology; Estradiol - analogs & derivatives; Estradiol - pharmacology; Estradiol - therapeutic use; Estrogen Antagonists - pharmacology; Estrogen Antagonists - therapeutic use; Female; General aspects; Humans; Medical sciences; Mitosis - drug effects; Pharmacology. Drug treatments; Polyunsaturated Alkamides; Tamoxifen - analogs & derivatives; Tamoxifen - therapeutic use; Time Factors; Antineoplastic agent; Human; Cell proliferation; Antiestrogen; In vitro; Tamoxifene; Resistance; Epidermal growth factor; Cell line; Treatment; Paracrine secretion; Mammary gland; Inhibition; Tumor cell
• ISSN: 0277-5379
• DOI: 10.1016/0277-5379(89)90051-5

A potential mechanism is described by which a growth factor may prevent the action of antiestrogens or reactivate 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 (E 2) stimulated cell proliferation in a dose-related fashion. However, in the presence of both E 2 and EGF, these two antiestrogens inhibited E 2 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.