title: Potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U844, University of Montpellier I, Montpellier F-34091, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Bossard
authors.forename: Muriel
authors.initials: M
authors.lastname: Busson
authors.forename: David
authors.initials: D
authors.lastname: Vindrieux
authors.forename: Françoise
authors.initials: F
authors.lastname: Gaudin
authors.forename: Véronique
authors.initials: V
authors.lastname: Machelon
authors.forename: Madly
authors.initials: M
authors.lastname: Brigitte
authors.forename: Carine
authors.initials: C
authors.lastname: Jacquard
authors.forename: Arnaud
authors.initials: A
authors.lastname: Pillon
authors.forename: Patrick
authors.initials: P
authors.lastname: Balaguer
authors.forename: Karl
authors.initials: K
authors.lastname: Balabanian
authors.forename: Gwendal
authors.initials: G
authors.lastname: Lazennec
mesh_terms: D049109:Cell Proliferation; D047629:Estrogen Receptor beta / Q000235:genetics / Q000502:physiology*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D047629:Estrogen Receptor beta; D016160:Retinoblastoma Protein