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Deficiency of ER beta and prostate tumorigenesis in FGF8b transgenic mice

På svenska

Author

  • Teresa Elo
  • Lan Yu
  • Eeva Valve
  • Sari Makela
  • Pirkko Härkönen

Summary, in English

Estrogens contribute to the development and growth of the prostate and are implicated in prostate tumorigenesis. In their target tissues, estrogens mediate their effects via estrogen receptor alpha (ER alpha (ESR1)) and beta (ER beta (ESR2)). Hyperplasia and decreased differentiation of epithelial cells in the prostate have been reported in ER beta knockout (BERKO) mice. Herein, we studied the effect of ER beta deficiency on prostate tumorigenesis by crossing BERKOFVB mice with prostate-targeted human fibroblast growth factor 8b transgenic (FGF8b-Tg) mice. Consistent with results described in our previous report, the prostates of 1-year-old FGF8b-Tg mice displayed stromal aberrations, prostatic intraepithelial neoplasia (mPIN) lesions, inflammation, and occasionally cancer. The prostates of BERKOFVB mice exhibited mild epithelial hypercellularity and inflammation. The prostate phenotypes of FGF8b-Tg-BERKOFVB mice closely resembled those of FGF8b-Tg mice. However, mucinous metaplasia, indicated by Goblet-like cells in the epithelium, was significantly more frequent in the prostates of FGF8b-Tg-BERKOFVB mice when compared with FGF8b-Tg mice. Furthermore, compared with FGF8b-Tg mice, there was a tendency for increased frequency of inflammation but milder hyperplasias in the prostate stroma of FGF8b-Tg-BERKOFVB mice. The expression levels of mRNAs for FGF8b-regulated genes including osteopontin (Spp1), connective tissue growth factor (Ctgf), fibroblast growth factor receptors (Fgfrs), and steroid hormone receptors and cytokines were similar in the prostates of FGF8b-Tg and FGF8b-Tg-BERKOFVB mice. Our results indicate that ER beta plays a role in the differentiation of the prostatic epithelium and, potentially, in the defensive mechanism required for protection against inflammation but do not support a direct tumor-suppressive function of ER beta in the prostate of FGF8b-Tg mice.

Publishing year

2014

Language

English

Pages

677-690

Publication/Series

Endocrine-Related Cancer

Volume

21

Issue

4

Document type

Journal article

Publisher

Society for Endocrinology

Topic

  • Cancer and Oncology

Keywords

  • estrogen receptor beta
  • fibroblast growth factor 8b
  • transgenic mouse
  • prostate
  • tumorigenesis

Status

Published

ISBN/ISSN/Other

  • ISSN: 1479-6821