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Importance of Estrogenic Signaling and Its Mediated Receptors in Prostate Cancer

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2016 Sep 3
PMID 27589731
Citations 21
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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.

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References
1.
Wernert N, Gerdes J, Loy V, Seitz G, Scherr O, Dhom G . Investigations of the estrogen (ER-ICA-test) and the progesterone receptor in the prostate and prostatic carcinoma on immunohistochemical basis. Virchows Arch A Pathol Anat Histopathol. 1988; 412(4):387-91. DOI: 10.1007/BF00750267. View

2.
Marengo S, Chung L . An orthotopic model for the study of growth factors in the ventral prostate of the rat: effects of epidermal growth factor and basic fibroblast growth factor. J Androl. 1994; 15(4):277-86. View

3.
Bowman S, Barnes D, Blacklock N, Sullivan P . Regional variation of cytosol androgen receptors throughout the diseased human prostate gland. Prostate. 1986; 8(2):167-80. DOI: 10.1002/pros.2990080207. View

4.
Nicholson T, Ricke E, Marker P, Miano J, Mayer R, Timms B . Testosterone and 17β-estradiol induce glandular prostatic growth, bladder outlet obstruction, and voiding dysfunction in male mice. Endocrinology. 2012; 153(11):5556-65. PMC: 3473198. DOI: 10.1210/en.2012-1522. View

5.
Barrett-Connor E, Garland C, McPhillips J, Khaw K, Wingard D . A prospective, population-based study of androstenedione, estrogens, and prostatic cancer. Cancer Res. 1990; 50(1):169-73. View