title: Deficiency of ERβ and prostate tumorigenesis in FGF8b transgenic mice.
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 α (ERα (ESR1)) and β (ERβ (ESR2)). Hyperplasia and decreased differentiation of epithelial cells in the prostate have been reported in ERβ knockout (BERKO) mice. Herein, we studied the effect of ERβ 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 ERβ 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 ERβ in the prostate of FGF8b-Tg mice.
authors.affiliation: Departments of Cell Biology and AnatomyPharmacologyDrug Development and TherapeuticsTurku Center for Disease ModelingInstitute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandFunctional Foods ForumUniversity of Turku, Turku, FinlandDepartment of Laboratory MedicineMAS University Hospital, Lund University, Malmö, Sweden teresa.elo@utu.fi.
authors.forename: Teresa
authors.initials: T
authors.lastname: Elo
authors.affiliation: Departments of Cell Biology and AnatomyPharmacologyDrug Development and TherapeuticsTurku Center for Disease ModelingInstitute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandFunctional Foods ForumUniversity of Turku, Turku, FinlandDepartment of Laboratory MedicineMAS University Hospital, Lund University, Malmö, Sweden.
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.affiliation: Departments of Cell Biology and AnatomyPharmacologyDrug Development and TherapeuticsTurku Center for Disease ModelingInstitute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandFunctional Foods ForumUniversity of Turku, Turku, FinlandDepartment of Laboratory MedicineMAS University Hospital, Lund University, Malmö, Sweden.
authors.forename: Eeva
authors.initials: E
authors.lastname: Valve
authors.affiliation: Departments of Cell Biology and AnatomyPharmacologyDrug Development and TherapeuticsTurku Center for Disease ModelingInstitute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandFunctional Foods ForumUniversity of Turku, Turku, FinlandDepartment of Laboratory MedicineMAS University Hospital, Lund University, Malmö, SwedenDepartments of Cell Biology and AnatomyPharmacologyDrug Development and TherapeuticsTurku Center for Disease ModelingInstitute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandFunctional Foods ForumUniversity of Turku, Turku, FinlandDepartment of Laboratory MedicineMAS University Hospital, Lund University, Malmö, Sweden.
authors.forename: Sari
authors.initials: S
authors.lastname: Mäkelä
authors.affiliation: Departments of Cell Biology and AnatomyPharmacologyDrug Development and TherapeuticsTurku Center for Disease ModelingInstitute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandFunctional Foods ForumUniversity of Turku, Turku, FinlandDepartment of Laboratory MedicineMAS University Hospital, Lund University, Malmö, SwedenDepartments of Cell Biology and AnatomyPharmacologyDrug Development and TherapeuticsTurku Center for Disease ModelingInstitute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, FinlandFunctional Foods ForumUniversity of Turku, Turku, FinlandDepartment of Laboratory MedicineMAS University Hospital, Lund University, Malmö, Sweden.
authors.forename: Pirkko
authors.initials: P
authors.lastname: Härkönen
mesh_terms: D000818:Animals; D047629:Estrogen Receptor beta / Q000172:deficiency* / Q000235:genetics; D051525:Fibroblast Growth Factor 9 / Q000235:genetics; D015870:Gene Expression; D008297:Male; D008822:Mice, Transgenic; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D047629:Estrogen Receptor beta; C496459:FGF9 protein, human; D051525:Fibroblast Growth Factor 9
keywords: estrogen receptor beta; fibroblast growth factor 8b; prostate; transgenic mouse; tumorigenesis