Advanced

Deficiency of ER beta and prostate tumorigenesis in FGF8b transgenic mice

Elo, Teresa; Yu, Lan; Valve, Eeva; Makela, Sari and Härkönen, Pirkko LU (2014) In Endocrine-Related Cancer 21(4). p.677-690
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,... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
estrogen receptor beta, fibroblast growth factor 8b, transgenic mouse, prostate, tumorigenesis
in
Endocrine-Related Cancer
volume
21
issue
4
pages
677 - 690
publisher
Society for Endocrinology
external identifiers
  • wos:000344788200033
  • scopus:84905962524
ISSN
1479-6821
DOI
10.1530/ERC-13-0480
language
English
LU publication?
yes
id
db2d1ce3-478e-4a3a-8ae2-a55a7bb78e94 (old id 4871821)
date added to LUP
2015-01-07 10:54:33
date last changed
2017-01-01 04:03:24
@article{db2d1ce3-478e-4a3a-8ae2-a55a7bb78e94,
  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.},
  author       = {Elo, Teresa and Yu, Lan and Valve, Eeva and Makela, Sari and Härkönen, Pirkko},
  issn         = {1479-6821},
  keyword      = {estrogen receptor beta,fibroblast growth factor 8b,transgenic mouse,prostate,tumorigenesis},
  language     = {eng},
  number       = {4},
  pages        = {677--690},
  publisher    = {Society for Endocrinology},
  series       = {Endocrine-Related Cancer},
  title        = {Deficiency of ER beta and prostate tumorigenesis in FGF8b transgenic mice},
  url          = {http://dx.doi.org/10.1530/ERC-13-0480},
  volume       = {21},
  year         = {2014},
}