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Title: Estrogen inhibits cell cycle progression and retinoblastoma phosphorylation in rhesus ovarian surface epithelial cell culture

Abstract

Estrogen promotes the growth of some ovarian cancer cells at nanomolar concentrations, but has been shown to inhibit growth of normal ovarian surface epithelial (OSE) cells at micromolar concentrations (1μg/ml). OSE cells express the estrogen receptor (ER)-α, and are the source of 90% of various cancers. The potential sensitivity of OSE cells to estrogen stresses the importance of understanding the estrogen-dependent mechanisms at play in OSE proliferation and transformation, as well as in anticancer treatment. We investigated the effects of estradiol on cell proliferation in vitro, and demonstrate an intracellular locus of action of estradiol in cultured rhesus ovarian surface epithelial (RhOSE) cells. We show that ovarian and breast cells are growth-inhibited by micromolar concentration of estradiol and that this inhibition correlates with estrogen receptor expression. We further show that normal rhesus OSE cells do not activate ERK or Akt in response to estradiol nor does estradiol block the ability of serum to stimulate ERK or induce cyclin D expression. Contrarily, estradiol inhibits serum-dependent retinoblastoma protein (Rb) phosphorylation and blocks DNA synthesis. This inhibition does not formally arrest cells and is reversible within hours of estrogen withdrawal. Our data are consistent with growth inhibition by activation of Rb and indicatemore » that sensitivity to hormone therapy in anticancer treatment can be modulated by cell cycle regulators downstream of the estrogen receptor.« less

Authors:
; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
945245
Report Number(s):
PNNL-SA-40207
Journal ID: ISSN 0303-7207; MCEND6; TRN: US200902%%1276
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Molecular and Cellular Endocrinology, 208(1-2):1-10; Journal Volume: 208; Journal Issue: 1-2
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 98 NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL PROTECTION; CELL CULTURES; CELL CYCLE; CELL PROLIFERATION; DNA; ESTRADIOL; ESTROGENS; GROWTH; HORMONES; IN VITRO; INHIBITION; MAMMARY GLANDS; NEOPLASMS; PHOSPHORYLATION; PROLIFERATION; PROTEINS; RUTHERFORD BACKSCATTERING SPECTROSCOPY; SENSITIVITY; STRESSES; SYNTHESIS; THERAPY; antiestrogen; estrogen; ERK; OSE; proliferations; Rb

Citation Formats

Wright, Jay W., Stouffer, Richard L., and Rodland, Karin D. Estrogen inhibits cell cycle progression and retinoblastoma phosphorylation in rhesus ovarian surface epithelial cell culture. United States: N. p., 2003. Web. doi:10.1016/j.mce.2003.08.001.
Wright, Jay W., Stouffer, Richard L., & Rodland, Karin D. Estrogen inhibits cell cycle progression and retinoblastoma phosphorylation in rhesus ovarian surface epithelial cell culture. United States. doi:10.1016/j.mce.2003.08.001.
Wright, Jay W., Stouffer, Richard L., and Rodland, Karin D. Fri . "Estrogen inhibits cell cycle progression and retinoblastoma phosphorylation in rhesus ovarian surface epithelial cell culture". United States. doi:10.1016/j.mce.2003.08.001.
@article{osti_945245,
title = {Estrogen inhibits cell cycle progression and retinoblastoma phosphorylation in rhesus ovarian surface epithelial cell culture},
author = {Wright, Jay W. and Stouffer, Richard L. and Rodland, Karin D.},
abstractNote = {Estrogen promotes the growth of some ovarian cancer cells at nanomolar concentrations, but has been shown to inhibit growth of normal ovarian surface epithelial (OSE) cells at micromolar concentrations (1μg/ml). OSE cells express the estrogen receptor (ER)-α, and are the source of 90% of various cancers. The potential sensitivity of OSE cells to estrogen stresses the importance of understanding the estrogen-dependent mechanisms at play in OSE proliferation and transformation, as well as in anticancer treatment. We investigated the effects of estradiol on cell proliferation in vitro, and demonstrate an intracellular locus of action of estradiol in cultured rhesus ovarian surface epithelial (RhOSE) cells. We show that ovarian and breast cells are growth-inhibited by micromolar concentration of estradiol and that this inhibition correlates with estrogen receptor expression. We further show that normal rhesus OSE cells do not activate ERK or Akt in response to estradiol nor does estradiol block the ability of serum to stimulate ERK or induce cyclin D expression. Contrarily, estradiol inhibits serum-dependent retinoblastoma protein (Rb) phosphorylation and blocks DNA synthesis. This inhibition does not formally arrest cells and is reversible within hours of estrogen withdrawal. Our data are consistent with growth inhibition by activation of Rb and indicate that sensitivity to hormone therapy in anticancer treatment can be modulated by cell cycle regulators downstream of the estrogen receptor.},
doi = {10.1016/j.mce.2003.08.001},
journal = {Molecular and Cellular Endocrinology, 208(1-2):1-10},
number = 1-2,
volume = 208,
place = {United States},
year = {Fri Oct 31 00:00:00 EST 2003},
month = {Fri Oct 31 00:00:00 EST 2003}
}