Bone Abstracts

Prostate cancer is a commonly diagnosed malignancy in Europe. Bone is one of the common metastasis sites. There is increasing evidence for estrogen involvement in the prostate tumorigenesis. ERβ knockout (BERKO) mice have been reported to have anti-proliferative, anti-inflammatory and potential anti-tumorigenic functions of ERβ. However, prostate phenotype of BERKO mice has been under debate.

The potential effect of ERβ on prostate tumorgenesis was studied by crossing BERKO mice with prostated targeted fibroblast growth factor 8b (Fgf8b-Tg) mice. Fgf8b-Tg mice develop advancing stromal and epithelial changes in the prostate that slowly progress to prostatic intraepithelial neoplasia (PIN) lesions and to prostate cancer with mixed features of adenocarcinoma and sarcoma at old age. In addition, androgen receptor staining was decreased in the transformed epithelium and in the hypercellular stroma but strongly increased in the sarcoma-like lesions of Fgf8b-Tg mice. Prostate phenotypes of 1- year-old WT, Fgf8b-Tg, BERKO and Fgf8b-Tg-BERKO were analyzed. Fgf8b-Tg mice contained similar change as previously reported, including stromal aberration, PIN lesion, inflammation and cancer. The prostate of BERKO mice contained mild epithelial hypercellularity and inflammation, but not neoplastic changes. Prostate phenotype of Fgf8b-Tg-BERKO mice was mostly similar to that of Fgf8b-Tg mice. However, mucinous metaplasia was statistically significantly more frequent in the prostate of Fgf8b-Tg-BERKO mice than in the Fgf8b-Tg mice. In addition, inflammation and stromal and epithelial hypercellularity were slightly more frequent in the prostate of Fgf8b-Tg-BERKO than in the Fgf8b-Tg mice. Our results suggest that ERβ could have a role in differentiation of the prostatic epithelium and in the protection from inflammation, but do not provide evidence for a direct role of ERβ as a tumor suppressor.