5α-reductase type 3 expression in human benign and malignant tissues: A comparative analysis during prostate cancer progression

Alejandro Godoy, Elzbieta Kawinski, Yun Li, Daizo Oka, Borislav Alexiev, Faris Azzouni, Mark A. Titus, James L. Mohler

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Background A third isozyme of human 5α-steroid reductase, 5α-reductase-3, was identified in prostate tissue at the mRNA level. However, the levels of 5α-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 5α-reductase-3 protein in 18 benign and 26 malignant human tissue types using immunostaining analyses. Results and ConclusionS In benign tissues, 5α-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 5α-reductase-3 among human tissues. In malignant tissues, 5α-reductase-3 immunostaining was ubiquitous but particularly over-expressed in some cancers compared to their benign counterparts, which suggests a potential role for 5α-reductase-3 as a biomarker of malignancy. In benign prostate, 5α-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), 5α-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), 5α-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 5α-reductase-3 in human tissues may prove useful for development of treatment for benign prostatic enlargement and prevention and treatment of CaP.

Original languageEnglish (US)
Pages (from-to)1033-1046
Number of pages14
JournalProstate
Volume71
Issue number10
DOIs
StatePublished - Jul 2011

Keywords

  • 5α-reductases
  • androgen metabolism
  • benign prostatic hyperplasia
  • castration-recurrent prostate cancer
  • dihydrotestosterone

ASJC Scopus subject areas

  • Oncology
  • Urology

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