Prostatic hormonal carcinogenesis is mediated by in situ estrogen production and estrogen receptor alpha signaling - PubMed (original) (raw)
. 2008 May;22(5):1512-20.
doi: 10.1096/fj.07-9526com. Epub 2007 Nov 30.
Affiliations
- PMID: 18055862
- DOI: 10.1096/fj.07-9526com
Prostatic hormonal carcinogenesis is mediated by in situ estrogen production and estrogen receptor alpha signaling
William A Ricke et al. FASEB J. 2008 May.
Abstract
It was recently demonstrated that antiestrogens prevented prostate cancer (PRCA) in men. The source of estradiol (E2) that contributes to carcinogenesis, as well as the selected estrogen receptor (ER) signaling pathway, is unknown. To evaluate estrogen's effects in carcinogenesis, we developed a new model of PRCA utilizing testosterone and E2 to stimulate PRCA. To determine whether local in situ production of E2 affected incidence of PRCA, aromatase-knockout (ArKO) mice were evaluated. In contrast to the wild-type mice, ArKO mice had reduced incidences of PRCA, which implicates in situ production of E2 as an important determinant of PRCA. To determine whether E2-mediated responses were due to ER alpha or ER beta signaling, ER alpha-knockout (alphaERKO) or ERbeta-knockout (betaERKO) mice were used. Prostates from betaERKO mice underwent biochemical and histological carcinogenesis similar to wild-type mice, whereas prostates from alphaERKO mice remained free of pathology. These data suggest that effective prevention of carcinogenesis will require antagonism of ER alpha but not ER beta. This mouse model provides a means to examine genetic gain and loss of function and determine the efficacy of therapeutics on prostatic carcinogenesis.
Comment in
- Regarding "Prostatic hormonal carcinogenesis is mediated by in situ estrogen production and estrogen receptor alpha signaling".
Friedman AE. Friedman AE. FASEB J. 2009 May;23(5):1285; author reply 1285-6. doi: 10.1096/fj.09-0502LTR. FASEB J. 2009. PMID: 19406847 No abstract available.
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