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Deficiency of ER beta and prostate tumorigenesis in FGF8b transgenic mice

In English

Författare

  • 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.

Publiceringsår

2014

Språk

Engelska

Sidor

677-690

Publikation/Tidskrift/Serie

Endocrine-Related Cancer

Volym

21

Issue

4

Dokumenttyp

Artikel i tidskrift

Förlag

Society for Endocrinology

Ämne

  • Cancer and Oncology

Nyckelord

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

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1479-6821