Deficiency of ER beta and prostate tumorigenesis in FGF8b transgenic mice
نویسندگان
چکیده
22 Estrogens contribute to the development and growth of the prostate and are implicated in prostate 23 tumorigenesis. In their target tissues, estrogens mediate their effects via estrogen receptor alpha 24 (ERa) and beta (ERb). Hyperplasia and decreased differentiation of epithelial cells in the prostate 25 have been reported in ERb knockout (BERKO) mice. We studied here the effect of ERb deficiency 26 on prostate tumorigenesis by crossing BERKOFVB mice with prostate-targeted fibroblast growth 27 factor 8b transgenic (FGF8b-Tg) mice. Consistent with our previous report, the prostates of one28 year-old FGF8b-Tg mice displayed stromal aberrations, prostatic intraepithelial neoplasia (mPIN) 29 lesions, inflammation and occasionally cancer. The prostates of BERKOFVB mice contained mild 30 epithelial hypercellularity and inflammation. The prostate phenotypes of FGF8b-Tg-BERKOFVB 31 mice closely resembled those of FGF8b-Tg mice. However, mucinous metaplasia, indicated by 32 Goblet-like cells in the epithelium, was significantly more frequent in the prostates of FGF8b-Tg33 BERKOFVB mice than FGF8b-Tg mice. Furthermore, compared to FGF8b-Tg mice, there was a 34 tendency for increased frequency of inflammation but milder hyperplasias in the prostate stroma of 35 FGF8b-Tg-BERKOFVB mice. The expression levels of mRNAs for FGF8b-regulated genes 36 including osteopontin (Spp1), connective tissue growth factor (Ctgf), fibroblast growth factor 37 receptors (Fgfrs), and for steroid hormone receptors and cytokines were similar in the prostates of 38 FGF8b-Tg and FGF8b-Tg-BERKOFVB mice. Our results suggest that ERb plays a role in 39 differentiation of the prostatic epithelium and potentially in protection from inflammation but do 40 not support a direct tumor suppressive function of ERb in the prostate of FGF8b-Tg mice. 41
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