Role of Estrogen Receptor β, G-Protein Coupled Estrogen Receptor and Estrogen-Related Receptors in Endometrial and Ovarian Cancer

SIMPLE SUMMARY: Despite new therapeutic approaches, ovarian cancer is still the most lethal gynecological cancer that is mainly diagnosed in its advanced stages. Contrarily, endometrial cancer is often detected in its early stages. However, in the cases of recurrence or advanced disease, treatment options are still limited. Both the ovary and endometrium are affected by estrogens and their receptors. The well-known estrogen receptor α (ERα) mediates estrogen effects such as the activation of cell proliferation. In contrast, the functions of the later discovered ERs, ERβ and GPER1, and of estrogen-related receptors (ERRs), are less understood. Increasing evidence suggests them to be involved in tumor development, progression, and metastasis. This article provides a summary and update of the current findings on the role of these receptors in ovarian and endometrial cancer to show at which points further research is reasonable and might change the future of their treatment. ABSTRACT: Ovarian and endometrial cancers are affected by estrogens and their receptors. It has been long known that in different types of cancers, estrogens activate tumor cell proliferation via estrogen receptor α (ERα). In contrast, the role of ERs discovered later, including ERβ and G-protein-coupled ER (GPER1), in cancer is less well understood, but the current state of knowledge indicates them to have a considerable impact on both cancer development and progression. Moreover, estrogen related receptors (ERRs) have been reported to affect pathobiology of many tumor types. This article provides a summary and update of the current findings on the role of ERβ, GPER1, and ERRs in ovarian and endometrial cancer. For this purpose, original research articles on the role of ERβ, GPER1, and ERRs in ovarian and endometrial cancers listed in the PubMed database have been reviewed.