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

Abstract

Estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) 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. ERβ has multiple isoforms that show differing association with prognosis. Expression levels of the full length ERβ1 isoform are often lower in aggressive cancers as compared to normal tissue. High ERβ1 expression is associated with improved overall survival in women with breast cancer. The promise of ERβ activation, as a potential targeted therapy, is based on concurrent activation of multiple tumor suppressor pathways with few side effects compared to chemotherapy. Thus, ERβ 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 ERα agonist activity, will be necessary to fully harness the potential of ERβ.

Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer

“…5). These pathways are known to be dysregulated in multiple cancer types including hormone independent melanoma and non-melanoma skin cancers and are often targets for chemotherapeutic intervention (Chan et al 2018 ; Dika et al 2019 ; Hua et al 2018 ; Karayazi Atici et al 2020 ; Mal et al 2020 ; Pisano et al 2021 ; Porter et al 2019 ; Rajabi et al 2017 ; Xiao et al 2019 ). As 3+ exposure at the environmentally relevant level of 100 nM for 48 h was found to suppress the expression of ERα mRNA and protein in MCF-7 cells and bind competitively to its hormone binding domain with K i of 5 nM, modulating its downstream signaling (Davey et al 2007 ; Stoica et al 2000 ; Watson and Yager 2007 ).…”

Effect of the Intake of Isoflavones on Risk Factors of Breast Cancer—A Systematic Review of Randomized Controlled Intervention Studies

“…Second, isoflavones may alter estrogen metabolism away from cancerous metabolites (16-α-hydroxyl metabolites) towards 2-hydroxy estrogen metabolites with lower estrogen activity. Third, due to structural similarities to human 17β-estradiol, isoflavones can bind to estrogen receptors (ER), preferentially to ER-β, which suppresses the transcription of many genes involved in cell growth and inflammation, thereby diminishing the estrogenic effects induced by ERα [ 8 , 9 ].…”

Survival Is Related to Estrogen Signal Transduction Pathway Activity in Postmenopausal Women Diagnosed with High-Grade Serous Ovarian Carcinoma

“…Thus, normal ER pathway activity, which is necessary for differentiated cell functions in healthy cells, is lost in HGSC. Alternatively, the differences in survival may result from preferential activity of the ER-α transcription factor over the ER-β transcription factor [22,23]. ER-β mediated signaling is tumor suppressing while ER-α mediated signaling results in increased proliferation and thus acts as a tumor promotor.…”