title: 5α-reductase type 3 expression in human benign and malignant tissues: a comparative analysis during prostate cancer progression.
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.
  
  
  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.
authors.affiliation: Department of Urology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Godoy
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kawinski
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Daizo
authors.initials: D
authors.lastname: Oka
authors.forename: Borislav
authors.initials: B
authors.lastname: Alexiev
authors.forename: Faris
authors.initials: F
authors.lastname: Azzouni
authors.forename: Mark A
authors.initials: MA
authors.lastname: Titus
authors.forename: James L
authors.initials: JL
authors.lastname: Mohler
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology; D011467:Prostate / Q000201:enzymology* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase