Epigenetic Modulation of Estrogen Receptor Signaling in Ovarian Cancer.

Ovarian cancer remains one of the leading causes of cancer-related deaths in women. There are several processes that are described to have a causal relationship in ovarian cancer development, progression, and metastasis formation, that occur both at the genetic and epigenetic level. One of the mechanisms involved in its pathogenesis and progression is estrogen signaling. Estrogen receptors (ER) α, ERβ, and G-protein coupled estrogen receptor 1 (GPER1), in concert with various coregulators and pioneer transcription factors, mediate the effects of estrogens primarily by the transcriptional regulation of estrogen responsive genes, thereby exerting pleiotropic effects including the regulation of cellular proliferation and apoptosis. The expression and activity of estrogen receptors and their coregulators have been demonstrated to be regulated by epigenetic mechanisms like histone modifications and DNA methylation. Here, we intend to summarize and to provide an update on the current understanding of epigenetic mechanisms regulating estrogen signaling and their role in ovarian cancer. For this purpose, we reviewed publications on this topic listed in the PubMed database. Finally, we assess to which extent drugs acting on the epigenetic level might be suitable for the treatment of ovarian cancer.