The growth response of BG-1 ovarian carcinoma cells to estradiol, 4OH-tamoxifen, and tamoxifen: Evidence for intrinsic antiestrogen activation

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 ca...

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Veröffentlicht in:Gynecologic oncology 1991-09, Vol.42 (3), p.245-249
Hauptverfasser: Pavlik, Edward J., Nelson, Katherine, van Nagell, John R., Gallion, Holly S., Donaldson, Elvis S., DePriest, P., Meares, Katherine
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container_end_page 249
container_issue 3
container_start_page 245
container_title Gynecologic oncology
container_volume 42
creator Pavlik, Edward J.
Nelson, Katherine
van Nagell, John R.
Gallion, Holly S.
Donaldson, Elvis S.
DePriest, P.
Meares, Katherine
van Nagell, John R.
description 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 ~7× 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 ×. Phenol red-free media containing 10% FCS (
doi_str_mv 10.1016/0090-8258(91)90353-7
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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 ~7× 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 ×. Phenol red-free media containing 10% FCS (&lt;20 pg estradiol (E 2)/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. E 2 (10 n M) 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 ×). The metabolically active AES (4OH-tamoxifen, 50 n M) reduced E 2-stimulated MCF-7 growth to 3–4 ×, while tamoxifen (50 n M) had no effect. Rescue with 10 μM E 2 fully overcame the AES inhibition of MCF-7 proliferation. In contrast, BG-1 cells experienced significant E 2-stimulated growth reductions in the presence of either 4OH-tamoxifen or tamoxifen. E 2 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. 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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 ~7× 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 ×. Phenol red-free media containing 10% FCS (&lt;20 pg estradiol (E 2)/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. E 2 (10 n M) 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 ×). 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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 ~7× 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 ×. Phenol red-free media containing 10% FCS (&lt;20 pg estradiol (E 2)/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. E 2 (10 n M) 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 ×). The metabolically active AES (4OH-tamoxifen, 50 n M) reduced E 2-stimulated MCF-7 growth to 3–4 ×, while tamoxifen (50 n M) had no effect. Rescue with 10 μM E 2 fully overcame the AES inhibition of MCF-7 proliferation. In contrast, BG-1 cells experienced significant E 2-stimulated growth reductions in the presence of either 4OH-tamoxifen or tamoxifen. E 2 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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>1955187</pmid><doi>10.1016/0090-8258(91)90353-7</doi><tpages>5</tpages></addata></record>
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subjects Carcinoma - pathology
Cell Division - drug effects
Culture Media
Estradiol - pharmacology
Estrogen Antagonists - pharmacology
Estrogens - pharmacology
Female
Humans
Ovarian Neoplasms - pathology
Tamoxifen - analogs & derivatives
Tamoxifen - pharmacology
Tumor Cells, Cultured
title The growth response of BG-1 ovarian carcinoma cells to estradiol, 4OH-tamoxifen, and tamoxifen: Evidence for intrinsic antiestrogen activation
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