Potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer.

Ovarian cancer is the gynecological cancer exhibiting the highest morbidity and improvement of treatments is still required. Previous studies have shown that Estrogen-receptor beta (ERβ) levels decreased along with ovarian carcinogenesis. Here, we present evidence that reintroduction of ERβ in BG-1...

Full description

Bibliographic Details
Main Authors: Carine Bossard, Muriel Busson, David Vindrieux, Françoise Gaudin, Véronique Machelon, Madly Brigitte, Carine Jacquard, Arnaud Pillon, Patrick Balaguer, Karl Balabanian, Gwendal Lazennec
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3435304?pdf=render
_version_ 1818289802742595584
author Carine Bossard
Muriel Busson
David Vindrieux
Françoise Gaudin
Véronique Machelon
Madly Brigitte
Carine Jacquard
Arnaud Pillon
Patrick Balaguer
Karl Balabanian
Gwendal Lazennec
author_facet Carine Bossard
Muriel Busson
David Vindrieux
Françoise Gaudin
Véronique Machelon
Madly Brigitte
Carine Jacquard
Arnaud Pillon
Patrick Balaguer
Karl Balabanian
Gwendal Lazennec
author_sort Carine Bossard
collection DOAJ
description Ovarian cancer is the gynecological cancer exhibiting the highest morbidity and improvement of treatments is still required. Previous studies have shown that Estrogen-receptor beta (ERβ) levels decreased along with ovarian carcinogenesis. Here, we present evidence that reintroduction of ERβ in BG-1 epithelial ovarian cancer cells, which express ERα, leads in vitro to a decrease of basal and estradiol-promoted cell proliferation. ERβ reduced the frequency of cells in S phase and increased the one of cells in G2/M phase. At the molecular level, we found that ERβ downregulated total retinoblastoma (Rb), phosphorylated Rb and phospho-AKT cellular content as well as cyclins D1 and A2. In addition, ERβ had a direct effect on ERα, by strongly inhibiting its expression and activity, which could explain part of the anti-proliferative action of ERβ. By developing a novel preclinical model of ovarian cancer based on a luminescent orthotopic xenograft in athymic Nude mice, we further revealed that ERβ expression reduces tumor growth and the presence of tumor cells in sites of metastasis, hence resulting in improved survival of mice. Altogether, these findings unveil a potential tumor-suppressor role of ERβ in ovarian carcinogenesis, which could be of potential clinical relevance for the selection of the most appropriate treatment for patients.
first_indexed 2024-12-13T02:18:04Z
format Article
id doaj.art-4cc3ef8933bb40fe894e110a313d5f1f
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-13T02:18:04Z
publishDate 2012-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-4cc3ef8933bb40fe894e110a313d5f1f2022-12-22T00:02:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4478710.1371/journal.pone.0044787Potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer.Carine BossardMuriel BussonDavid VindrieuxFrançoise GaudinVéronique MachelonMadly BrigitteCarine JacquardArnaud PillonPatrick BalaguerKarl BalabanianGwendal LazennecOvarian cancer is the gynecological cancer exhibiting the highest morbidity and improvement of treatments is still required. Previous studies have shown that Estrogen-receptor beta (ERβ) levels decreased along with ovarian carcinogenesis. Here, we present evidence that reintroduction of ERβ in BG-1 epithelial ovarian cancer cells, which express ERα, leads in vitro to a decrease of basal and estradiol-promoted cell proliferation. ERβ reduced the frequency of cells in S phase and increased the one of cells in G2/M phase. At the molecular level, we found that ERβ downregulated total retinoblastoma (Rb), phosphorylated Rb and phospho-AKT cellular content as well as cyclins D1 and A2. In addition, ERβ had a direct effect on ERα, by strongly inhibiting its expression and activity, which could explain part of the anti-proliferative action of ERβ. By developing a novel preclinical model of ovarian cancer based on a luminescent orthotopic xenograft in athymic Nude mice, we further revealed that ERβ expression reduces tumor growth and the presence of tumor cells in sites of metastasis, hence resulting in improved survival of mice. Altogether, these findings unveil a potential tumor-suppressor role of ERβ in ovarian carcinogenesis, which could be of potential clinical relevance for the selection of the most appropriate treatment for patients.http://europepmc.org/articles/PMC3435304?pdf=render
spellingShingle Carine Bossard
Muriel Busson
David Vindrieux
Françoise Gaudin
Véronique Machelon
Madly Brigitte
Carine Jacquard
Arnaud Pillon
Patrick Balaguer
Karl Balabanian
Gwendal Lazennec
Potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer.
PLoS ONE
title Potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer.
title_full Potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer.
title_fullStr Potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer.
title_full_unstemmed Potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer.
title_short Potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer.
title_sort potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer
url http://europepmc.org/articles/PMC3435304?pdf=render
work_keys_str_mv AT carinebossard potentialroleofestrogenreceptorbetaasatumorsuppressorofepithelialovariancancer
AT murielbusson potentialroleofestrogenreceptorbetaasatumorsuppressorofepithelialovariancancer
AT davidvindrieux potentialroleofestrogenreceptorbetaasatumorsuppressorofepithelialovariancancer
AT francoisegaudin potentialroleofestrogenreceptorbetaasatumorsuppressorofepithelialovariancancer
AT veroniquemachelon potentialroleofestrogenreceptorbetaasatumorsuppressorofepithelialovariancancer
AT madlybrigitte potentialroleofestrogenreceptorbetaasatumorsuppressorofepithelialovariancancer
AT carinejacquard potentialroleofestrogenreceptorbetaasatumorsuppressorofepithelialovariancancer
AT arnaudpillon potentialroleofestrogenreceptorbetaasatumorsuppressorofepithelialovariancancer
AT patrickbalaguer potentialroleofestrogenreceptorbetaasatumorsuppressorofepithelialovariancancer
AT karlbalabanian potentialroleofestrogenreceptorbetaasatumorsuppressorofepithelialovariancancer
AT gwendallazennec potentialroleofestrogenreceptorbetaasatumorsuppressorofepithelialovariancancer