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.