5α-Reductase Type 3 Expression in Human Benign and Malignant Tissues: A Comparative Analysis During Prostate Cancer Progression

BACKGROUND. A third isozyme of human 5 alpha-steroid reductase, 5 alpha-reductase-3, was identified in prostate tissue at the mRNA level. However, the levels of 5 alpha-reductase-3 protein expression and its cellular localization in human tissues remain unknown. METHODS. A specific monoclonal antibody was developed, validated, and used to characterize for the first time the expression of 5 alpha-reductase-3 protein in 18 benign and 26 malignant human tissue types using immunostaining analyses. RESULTS AND CONCLUSIONS. In benign tissues, 5 alpha-reductase-3 immunostaining was high in conventional androgen-regulated human tissues, such as skeletal muscle and prostate. However, high levels of expression also were observed in non-conventional androgen-regulated tissues, which suggest either multiples target tissues for androgens or different functions of 5 alpha-reductase-3 among human tissues. In malignant tissues, 5 alpha-reductase-3 immunostaining was ubiquitous but particularly over-expressed in some cancers compared to their benign counterparts, which suggests a potential role for 5 alpha-reductase-3 as a biomarker of malignancy. In benign prostate, 5 alpha-reductase-3 immunostaining was localized to basal epithelial cells, with no immunostaining observed in secretory/luminal epithelial cells. In high-grade prostatic intraepithelial neoplasia (HGPIN), 5 alpha-reductase-3 immunostaining was localized in both basal epithelial cells and neoplastic epithelial cells characteristic of HGPIN. In androgen-stimulated and castration-recurrent prostate cancer (CaP), 5 alpha-reductase-3 immunostaining was present in most epithelial cells and at similar levels, and at levels higher than observed in benign prostate. Analyses of expression and functionality of 5 alpha-reductase-3 in human tissues may prove useful for development of treatment for benign prostatic enlargement and prevention and treatment of CaP. Prostate 71: 1033-1046, 2011. (C) 2010 Wiley-Liss, Inc.