Extranuclear signaling by sex steroid receptors and clinical implications in breast cancer

Publication date: Available online 14 November 2017
Source:Molecular and Cellular Endocrinology
Author(s): Viroj Boonyaratanakornkit, Nalo Hamilton, Diana C. Márquez-Garbán, Prangwan Pateetin, Eileen M. McGowan, Richard J. Pietra
Estrogen and progesterone, play essential roles in the development and progression of breast cancer. Over 70% of breast cancers express estrogen receptors (ER) and progesterone receptors (PR), emphasizing the need for better understanding of ER and PR signaling. ER and PR are traditionally viewed as transcription factors and directly bind DNA to regulate gene networks. In addition to nuclear signaling, ER and PR mediate hormone-induced, rapid extranuclear signaling at the cell membrane or in the cytoplasm which initiates downstream signaling to regulate either rapid or extended cellular responses. Specialized membrane and cytoplasmic proteins may also initiate hormone-induced extranuclear signaling. Rapid extranuclear signaling converges with its nuclear counterpart to amplify ER/PR transcription and specify gene regulatory networks. This review summarizes current understanding and updates on ER and PR extranuclear signaling. Further investigation of ER/PR extranuclear signaling may lead to development of novel targeted therapeutics for breast cancer management.



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