Xenoestrogen regulation of ERα/ERβ balance in hormone-associated cancers

The hormone 17 beta-estradiol (E2) contributes to body homeostasis maintenance by regulating many different physiological functions in both male and female organs. E2 actions in reproductive and non-reproductive tissues rely on a complex net of nuclear and extra-nuclear signal transduction pathways triggered by at least two estrogen receptor subtypes (ER alpha and ER beta). Consequently, the de-regulation of E2:ER signaling contributes to the pathogenesis of many diseases including cancer. Among other factors, the ER alpha/ER beta, ratio is considered one of the pivotal mechanisms at the root of E2 action in cancer progression. Remarkably, several natural or synthetic exogenous chemicals, collectively called xenoestrogens, bind to ERs and interfere with their signals and intracellular functions. In this review, the molecular mechanism(s) through which xenoestrogens influence ER alpha and ER beta intracellular concentrations and the consequences of this influence on E2-related cancer will be discussed. (C) 2016 Elsevier Ireland Ltd. All rights reserved.