Derailed estrogen signaling and breast cancer: An authentic couple

Abstract

Estrogen or 17β-estradiol, a steroid hormone, plays a critical role in the development of mammary gland via acting through specific receptors. In particular, estrogen receptor-α (ERα) acts as a transcription factor and/or a signal transducer while participating in the development of mammary gland and breast cancer. Accumulating evidence suggests that the transcriptional activity of ERα is altered by the action of nuclear receptor coregulators and might be responsible, at least in part, for the development of breast cancer. In addition, this process is driven by various posttranslational modifications of ERα, implicating active participation of the upstream receptor modifyingenzymesin breast cancer progression. Emerging studies suggest that the biologicaloutcomeof breast cancer cells is also influenced by the cross talk between microRNA and ERα signaling, as well as by breast cancer stem cells. Thus, multiple regulatory controls ofERα rendermammaryepithelium at risk for transformationupon deregulation of normal homeostasis. Given the importance thatERα signaling has in breast cancer development, here we will highlight how the activity of ERα is controlled by various regulators in a spatial and temporal manner, impacting the progression of the disease. We will also discuss the possible therapeutic value of ERα modulators as alternative drug targets to retard the progression of breast cancer. © 2013 by The Endocrine Society.