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J Urol. 2011 Jan;185(1):305-14. doi: 10.1016/j.juro.2010.09.008.

Inhibition of aberrant androgen receptor induction of prostate specific antigen gene expression, cell proliferation and tumor growth by 17α-estradiol in prostate cancer.

Author information

  • 1Department of Medicine/Endocrinology, Weill Medical College of Cornell University, New York, New York 10065, USA. yuz2002@med.cornell.edu

Abstract

PURPOSE:

Androgen independent prostate cancer growth and metastasis are a major cause of prostate cancer death. Aberrant androgen receptor activation due to androgen receptor mutation is an important mechanism of androgen independence. We determined the effectiveness and mechanism of 17α-estradiol (Sigma®) in blocking aberrant androgen receptor activation due to androgen receptor mutation.

MATERIALS AND METHODS:

We used LNCaP and MDA Pca-2b prostatic tumor cells (ATCC®) containing a mutated androgen receptor and WT estrogen receptor β to test 17α-estradiol inhibition of aberrant androgen receptor activation of prostate specific antigen gene expression and cell growth. Cotransfection analysis was used to further elucidate the mechanism of 17α-estradiol action. Xenograft animals with an LNCaP prostate tumor were prepared to study the in vivo effect of 17α-estradiol on tumor growth inhibition.

RESULTS:

In LNCaP cells 17α-estradiol produced a dose dependent inhibition of cyproterone acetate (Sigma) or dihydrotestosterone induced prostate specific antigen gene expression. In MDA Pca-2b cells 17α-estradiol inhibited cortisol (Sigma) induced prostate specific antigen expression and blocked dihydrotestosterone and cortisol induced cell proliferation in LNCaP and MDA Pca-2b cells, respectively. Cotransfection analysis showed that 17α-estradiol inhibition of aberrant androgen receptor activation of prostate specific antigen gene expression was medicated via estrogen receptors. In xenograft mice with LNCaP prostate cancer 17α-estradiol but not 17β-estradiol (Sigma) significantly inhibited tumor growth, although each estrogen tended to decrease tumor growth.

CONCLUSIONS:

Results suggest that 17α-estradiol with less classic estrogenic activity is a potential therapeutic agent for androgen independent prostate cancer due to androgen receptor mutation.

Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

PMID:
21075385
[PubMed - indexed for MEDLINE]
PMCID:
PMC3039213
Free PMC Article

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