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Int. J. Mol. Sci. 2016, 17(9), 1434; doi:10.3390/ijms17091434

Importance of Estrogenic Signaling and Its Mediated Receptors in Prostate Cancer

Department of Anatomical and Cellular Pathology, State Key Laboratory of Oncology in Southern China, and Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong, China
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Authors to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 25 July 2016 / Revised: 16 August 2016 / Accepted: 23 August 2016 / Published: 31 August 2016
(This article belongs to the Collection Advances in Molecular Oncology)
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Abstract

Prostate cancer (PCa) treatment was first established by Huggins and Hodges in 1941, primarily described as androgen deprivation via interference of testicular androgen production. The disease remains incurable with relapse of hormone-refractory cancer after treatments. Epidemiological and clinical studies disclosed the importance of estrogens in PCa. Discovery of estrogen receptor ERβ prompted direct estrogenic actions, in conjunction with ERα, on PCa cells. Mechanistically, ERs upon ligand binding transactivate target genes at consensus genomic sites via interactions with various transcriptional co-regulators to mold estrogenic signaling. With animal models, Noble revealed estrogen dependencies of PCa, providing insight into potential uses of antiestrogens in the treatment. Subsequently, various clinical trials were conducted and molecular and functional consequences of antiestrogen treatment in PCa were delineated. Besides, estrogens can also trigger rapid non-genomic signaling responses initiated at the plasma membrane, at least partially via an orphan G-protein-coupled receptor GPR30. Activation of GPR30 significantly inhibited in vitro and in vivo PCa cell growth and the underlying mechanism was elucidated. Currently, molecular networks of estrogenic and antiestrogenic signaling via ERα, ERβ and GPR30 in PCa have not been fully deciphered. This crucial information could be beneficial to further developments of effective estrogen- and antiestrogen-based therapy for PCa patients. View Full-Text
Keywords: prostate cancer; estrogens; antiestrogens; estrogen receptors; ERα; ERβ; GPR30; GPER; fulvestrant prostate cancer; estrogens; antiestrogens; estrogen receptors; ERα; ERβ; GPR30; GPER; fulvestrant
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Lau, K.-M.; To, K.-F. Importance of Estrogenic Signaling and Its Mediated Receptors in Prostate Cancer. Int. J. Mol. Sci. 2016, 17, 1434.

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