title: The growth response of BG-1 ovarian carcinoma cells to estradiol, 4OH-tamoxifen, and tamoxifen: evidence for intrinsic antiestrogen activation.
abstract: The influence of estrogen (E) and antiestrogen (AES) on the in vitro growth of BG-1 ovarian carcinoma cells, which express steroid receptors was examined (K. R. Geisinger, T. E. Kute, M. J. Pettenati, C. E. Welander, Y. Dennard, L. A. Collins, and M. E. Berens, Characterization of a human ovarian carcinoma cell line with estrogen and progesterone receptors, Cancer 63, 280-288, 1989). All determinations were simultaneously referenced under similar conditions to MCF-7 cells, a well-established cell line for modeling hormonal responses in breast cancer. In "complete" media containing fetal calf serum (FCS, 10%), MCF-7 cell numbers increased approximately 7 x in 7 days, remaining at this level Days 8-15. In contrast, BG-1 cells achieved similar numbers by Day 7, but showed apparent exponential growth over Days 8-15 to 15-20 x. Phenol red-free media containing 10% FCS (less than 20 pg estradiol (E2)/ml by RIA) was used to assess responses to E and AES. Growth of both MCF-7 and BG-1 cells slowed in E-free media. E2 (10 nM) stimulated the growth of both cell lines, yet was responsible for exponential increases during Days 8-15 only in BG-1 cell numbers (50-70 x). The metabolically active AES (4OH-tamoxifen, 50 nM) reduced E2-stimulated MCF-7 growth to 3-4 x, while tamoxifen (50 nM) had no effect. Rescue with 10 microM E2 fully overcame the AES inhibition of MCF-7 proliferation. In contrast, BG-1 cells experienced significant E2-stimulated growth reductions in the presence of either 4OH-tamoxifen or tamoxifen. E2 was observed to rescue BG-1 cells from both of these antagonists. We conclude that BG-1 ovarian carcinoma cells respond in vitro to E and AES. Moreover, by virtue of responses to tamoxifen, BG-1 cells may have an intrinsic capacity to hydroxylate tamoxifen to its active metabolite. This property of ovarian carcinoma cells might be worth exploiting in the design of more effective combination chemotherapy regimens.
authors.affiliation: Department of Obstetrics and Gynecology, University of Kentucky Medical Center, Lexington 40536.
authors.forename: E J
authors.initials: EJ
authors.lastname: Pavlik
authors.forename: K
authors.initials: K
authors.lastname: Nelson
authors.forename: J R
authors.initials: JR
authors.lastname: van Nagell
authors.forename: H S
authors.initials: HS
authors.lastname: Gallion
authors.forename: E S
authors.initials: ES
authors.lastname: Donaldson
authors.forename: P
authors.initials: P
authors.lastname: DePriest
authors.forename: K
authors.initials: K
authors.lastname: Meares
authors.forename: J R
authors.initials: JR
authors.lastname: van Nagell
mesh_terms: D002277:Carcinoma / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D003470:Culture Media; D004965:Estrogen Antagonists; D004967:Estrogens; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol