Deficiency of ER beta and prostate tumorigenesis in FGF8b transgenic mice

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • Teresa Elo
  • Lan Yu
  • Eeva Valve
  • Sari Makela
  • Pirkko Härkönen
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • estrogen receptor beta, fibroblast growth factor 8b, transgenic mouse, prostate, tumorigenesis
Original languageEnglish
Pages (from-to)677-690
JournalEndocrine-Related Cancer
Volume21
Issue number4
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

Department affilation moved from v1000588 (Tumour Biology, Malmö) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:39:28.