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Publication : Reduced prostate branching morphogenesis in stromal fibroblast, but not in epithelial, estrogen receptor α knockout mice.

First Author  Chen M Year  2012
Journal  Asian J Androl Volume  14
Issue  4 Pages  546-55
PubMed ID  22609821 Mgi Jnum  J:330500
Mgi Id  MGI:6839874 Doi  10.1038/aja.2011.181
Citation  Chen M, et al. (2012) Reduced prostate branching morphogenesis in stromal fibroblast, but not in epithelial, estrogen receptor alpha knockout mice. Asian J Androl 14(4):546-55
abstractText  Early studies suggested that estrogen receptor alpha (ERalpha) is involved in estrogen-mediated imprinting effects in prostate development. We recently reported a more complete ERalpha knockout (KO) mouse model via mating beta-actin Cre transgenic mice with floxed ERalpha mice. These ACTB-ERalphaKO male mice showed defects in prostatic branching morphogenesis, which demonstrates that ERalpha is necessary to maintain proliferative events in the prostate. However, within which prostate cell type ERalpha exerts those important functions remains to be elucidated. To address this, we have bred floxed ERalpha mice with either fibroblast-specific protein (FSP)-Cre or probasin-Cre transgenic mice to generate a mouse model that has deleted ERalpha gene in either stromal fibroblast (FSP-ERalphaKO) or epithelial (pes-ERalphaKO) prostate cells. We found that circulating testosterone and fertility were not altered in FSP-ERalphaKO and pes-ERalphaKO male mice. Prostates of FSP-ERalphaKO mice have less branching morphogenesis compared to that of wild-type littermates. Further analyses indicated that loss of stromal ERalpha leads to increased stromal apoptosis, reduced expression of insulin-like growth factor-1 (IGF-1) and FGF10, and increased expression of BMP4. Collectively, we have established the first in vivo prostate stromal and epithelial selective ERalphaKO mouse models and the results from these mice indicated that stromal fibroblast ERalpha plays important roles in prostatic branching morphogenesis via a paracrine fashion. Selective deletion of the ERalpha gene in mouse prostate epithelial cells by probasin-Cre does not affect the regular prostate development and homeostasis.
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