A new perspective on estrogen receptor beta in ovarian cancer progression

Abstract

O the gynecological malignancies, epithelial ovarian cancer is the leading cause of death in the great majority of developed countries with more than 140,000 women dying from this cancer across the world in 2008. The importance of estrogen signaling in the development and progression of ovarian cancer has been assumed to be less significant than in breast or endometrial malignancies, although preclinical studies and clinical data have shown that not only normal ovaries but also many malignant ovarian tumors can be considered as endocrine related, and hormone-dependent. Estrogens exert their action through two estrogen receptors (ERα and ERβ) that are encoded by separate genes. In the healthy ovary, the levels of ERβ are high and predominate over ERα, being ERβ1, -β2, and -β5 the most represented isoforms. The majority of ovarian tumors also express ERβ, but few studies have examined the prognostic role of ERβ isoforms in ovarian cancer. We have recently shown a strong statistical association of cytoplasmic ERβ2 immunoreactivity with an unfavorable outcome in advanced serous ovarian cancer patients, a finding also reported in familial and sporadic breast cancer. The functional role of cytoplasmic ERβ2 is far from being elucidated, however preliminary data from our ongoing studies suggest that cytoplasmic protein accumulation may confer pro-survival advantages to ovarian cancer cells by inhibiting apoptotic pathways.