Estrogen Receptor Beta (ERβ): A Ligand Activated Tumor Suppressor

Estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta) belong to a superfamily of nuclear receptors called steroid hormone receptors, which, upon binding ligand, dimerize and translocate to the nucleus where they activate or repress the transcription of a large number of genes, thus modulating critical physiologic processes. ER beta has multiple isoforms that show differing association with prognosis. Expression levels of the full length ER beta 1 isoform are often lower in aggressive cancers as compared to normal tissue. High ER beta 1 expression is associated with improved overall survival in women with breast cancer. The promise of ER beta activation, as a potential targeted therapy, is based on concurrent activation of multiple tumor suppressor pathways with few side effects compared to chemotherapy. Thus, ER beta is a nuclear receptor with broad-spectrum tumor suppressor activity, which could serve as a potential treatment target in a variety of human cancers including breast cancer. Further development of highly selective agonists that lack ER alpha agonist activity, will be necessary to fully harness the potential of ER beta.