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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435304/ https://www.ncbi.nlm.nih.gov/pubmed/22970307 http://dx.doi.org/10.1371/journal.pone.0044787 |
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author | Bossard, Carine Busson, Muriel Vindrieux, David Gaudin, Françoise Machelon, Véronique Brigitte, Madly Jacquard, Carine Pillon, Arnaud Balaguer, Patrick Balabanian, Karl Lazennec, Gwendal |
author_facet | Bossard, Carine Busson, Muriel Vindrieux, David Gaudin, Françoise Machelon, Véronique Brigitte, Madly Jacquard, Carine Pillon, Arnaud Balaguer, Patrick Balabanian, Karl Lazennec, Gwendal |
author_sort | Bossard, Carine |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-3435304 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34353042012-09-11 Potential Role of Estrogen Receptor Beta as a Tumor Suppressor of Epithelial Ovarian Cancer Bossard, Carine Busson, Muriel Vindrieux, David Gaudin, Françoise Machelon, Véronique Brigitte, Madly Jacquard, Carine Pillon, Arnaud Balaguer, Patrick Balabanian, Karl Lazennec, Gwendal PLoS One Research Article 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. Public Library of Science 2012-09-06 /pmc/articles/PMC3435304/ /pubmed/22970307 http://dx.doi.org/10.1371/journal.pone.0044787 Text en © 2012 Bossard et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Bossard, Carine Busson, Muriel Vindrieux, David Gaudin, Françoise Machelon, Véronique Brigitte, Madly Jacquard, Carine Pillon, Arnaud Balaguer, Patrick Balabanian, Karl Lazennec, Gwendal Potential Role of Estrogen Receptor Beta as a Tumor Suppressor of Epithelial Ovarian Cancer |
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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435304/ https://www.ncbi.nlm.nih.gov/pubmed/22970307 http://dx.doi.org/10.1371/journal.pone.0044787 |
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