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Prostate Cancer pp 383–419Cite as

Biology and Clinical Relevance of Estrogen Receptors in Prostate Cancer

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Part of the book series: Protein Reviews ((PRON,volume 16))

Abstract

This review explores the function of estrogen receptors (ERs) and their signaling pathways, and their involvement in the pathogenesis and management of prostate cancer (PCa). We pay special attention to (1) traditional estrogen receptors (ERα and ERβ) and the alternate estrogen receptor, G protein-coupled receptor 30 (GPR30); (2) therapeutic utility of estrogen and antiestrogens; (3) impact of genetic variants of ERs on prostate cancer risk; (4) epigenetic regulation of ERs; (5) downstream signaling of ERs; (6) diagnostic and prognostic value of these receptors; and (7) interaction between ERβ and aryl hydrocarbon receptor or androgen receptor. We also explore (a) the expression patterns of ERs and their spliced isoforms during normal development and the development and progression of PCa; (b) the divergent roles of the estrogen receptors as tumor suppressors and tumor promoters; (c) the possibility of developmental origin of the disease; and (d) the regulation of estrogen receptors via epigenetic modifications such as DNA methylation, histone modification, and microRNA processing. We also review the potential clinical application of various phytoestrogens (genistein, equol, dihydrogenistein, and daidzein), selective estrogen-receptor modulators (SERMs: tamoxifen, toremifene, and raloxifene), pure estrogen antagonists (e.g., fulvestrant), and transdermal estradiol delivered as preventive agents and first-line therapies or combinatory agents. We highlight the need for further studies of the role of ERs in epithelial–mesenchymal transition, prostate stem/progenitor cell function, and cross talk with other nuclear receptors and address the prospect of devising strategies for primordial prevention of PCa through improvements in the understanding of estrogen imprinting in early life.

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Acknowledgment

We thank Nancy Voynow for her professional editing of this manuscript. This work was supported by grants from NIH (ES020988, ES019480, ES006096, CA15776, and CA112532 to SMH), CDMRP Department of Defense (PC094619 to PT) and VA (BX000675 to SMH), and an internal funding source from the University of Cincinnati Medical Center.

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  1. Department of Environmental Health, University of Cincinnati Medical Center, 3223 Eden Avenue, Kettering Lab Complex, Room 130, Cincinnati, OH, 45267, USA

    Shuk-Mei Ho Ph.D., Pheruza Tarapore Ph.D., Ming-Tsung Lee M.Phil. & Yuet-Kin Leung Ph.D.

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  1. Shuk-Mei Ho Ph.D.
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  2. Pheruza Tarapore Ph.D.
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Correspondence to Shuk-Mei Ho Ph.D. .

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  1. , Depts of Urology, and, Mayo Clinic College of Medicine, 200 1st Street SW., Rochester, 55905, Minnesota, USA

    Donald J. Tindall

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Ho, SM., Tarapore, P., Lee, MT., Leung, YK. (2013). Biology and Clinical Relevance of Estrogen Receptors in Prostate Cancer. In: Tindall, D. (eds) Prostate Cancer. Protein Reviews, vol 16. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6828-8_14

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