Duality of estrogen receptor β action in cancer progression

The physiological actions of estrogens are primarily mediated by the nuclear hormone receptors estrogen receptor alpha (ER alpha) and beta (ER beta). Activities of these nuclear steroid hormone receptors in etiology and progression of many hormone-responsive cancers are well-established, yet the specific role of each receptor, and their various expressed isoforms, in estrogen-responsive cancers remains unclear. Recent advances in nuclear receptor profiling, characterization of expressed splice variants, and the availability of new experimental cancer models, has extended the understanding of the complex interplay between the differentially expressed nuclear estrogen receptors. In this review, we discuss proposed roles of ER beta in several subtypes of cancers that lack significant ER alpha expression and define current understanding of how different ERs collaborate to regulate cellular processes.