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URL: https://pubmed.ncbi.nlm.nih.gov/21557268/

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

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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.

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Figures

👁 Fig. 1
Fig. 1
Validation of the RPCI-5αR3 antibody. A: 5α-reductase-3 mRNA expression level in LNCaP, C4-2, LAPC-4, and CWR-R1 cells. 5α-reductase-3 mRNA expression levels in the CaP cell lines were normalized to the level of expression of 5α-reductase-3 in the PWR-1E benign prostate epithelial cell line (discontinuous red line). B: PWR-1E, LNCaP, C4-2, LAPC-4, CWR-R1, and CHO-K1 protein lysates (50 μg) were immunoblotted and 5α-reductase-3 protein expression was detected using the RPCI-5αR3 antibody. C: CWR-R1 lysates (50 μg) were immunoblotted and 5α-reductase-3 protein expression was analyzed using RPCI-5αR3 antibody at a concentration of 1 μg/ml or SRD5A3 (Sigma) antibody at concentrations 1 μg/ml and 5 μg/ml. D: Immunostaining analyses were performed in CWR-R1 using the RPCI-5αR3 antibody. Preincubation of the RPCI-5αR3 antibody with the inhibitor peptide (1 and 10 μg/ml) confirmed specificity. Absence of primary antibody provided negative control (Control).
👁 Fig. 2
Fig. 2
5α-reductase-3 immunostaining in benign human tissues. High level expressing tissues (representative sections that demonstrate semi-quantitative data in Table I). In kidney A,B: 5α-reductase-3 expression was localized to the cytoplasm of the epithelial cells from some of the proximal and distal convoluted tubules (B, arrow). In myometrium C,D: 5α-reductase-3 immunostaining was located preferentially to the cytoplasm of the smooth muscle cells (D: arrow, fibers in transverse). In pancreas E,F: 5α-reductase-3 immunostaining was observed in some of the secretory cells from the acini (F, arrow). Bars: 30 μm.
👁 Fig. 3
Fig. 3
5α-reductase-3 immunostaining in benign human tissues. Moderate to low level expressing tissues (representative sections that demonstrate semi-quantitative data in Table I). In testes A,B: 5α-reductase-3 expression was localized to the cytoplasm of Leydig cells (B, arrow). In brain C: 5α-reductase-3 immunostaining was localized to the cytoplasm of neurons (D, arrow). Low levels of 5α-reductase-3 immunostaining were observed in the glandular epithelium of endometrium (E, arrow). 5α-reductase-3 was immunohistochemically undetectable in tonsil (F). Bars: 30 μm.
👁 Fig. 4
Fig. 4
5α-reductase-3 immunostaining in malignant human tissues. High level expressing tissues (representative sections that demonstrate semi-quantitative data in Table II). 5α-reductase-3 expression was localized mainly to the cytoplasm of the malignant epithelial cells from adenocarcinoma of the stomach (A), hepatocellular carcinoma of the liver (B), papillary carcinoma of the thyroid (C), endometroid adenocarcinoma of the uterus (D), and adenocarcinoma of the colon (E). Bar: 30 μm.
👁 Fig. 5
Fig. 5
5α-reductase-3 immunostaining in malignant human tissues. Moderate to low level expressing tissues (representative sections that demonstrate semi-quantitative data in Table II). Moderate to low levels of 5α-reductase-3 expression were observed in the cytoplasm of neoplastic epithelial cells from adenocarcinoma of the esophagus (A), clear cell renal cell carcinoma of the kidney (B), papillary carcinoma of the kidney (C), embryonal testicular carcinoma (D), adenocarcinoma of the lung (E), and medullary carcinoma of the thyroid (F). Negative 5α-reductase-3 immunostaining was observed in small cell carcinoma of the bladder (G), mesothelioma (H), and leiomyosarcoma (I). Bar: 30 μm.
👁 Fig. 6
Fig. 6
5α-reductase-3 immunostaining in androgen-stimulated benign prostate (AS-BP), androgen-stimulated high grade intraepithelial neoplasia (AS-HGPIN), androgen-stimulated CaP (AS-CaP), and castration-recurrent CaP (CR-CaP) tissue sections (representative sections that demonstrate quantitative data in Table III). 5α-reductase-3 immunostaining in AS-BP was observed primarily at the periphery of benign glands, which suggests 5α-reductase-3 expression in the basal cell compartment (B, C [arrows]) that was confirmed by co-localization of 5α-reductase-3 (brown cytoplasmic stain) and p63 (rednuclear stain) immunostaining (D). No to low levels of 5α-reductase-3 immunostaining were observed in benign luminal epithelial cells (B [arrowhead]). In HGPIN, 5α-reductase-3 immunostaining was located in both basal cells and hyperproliferative malignant luminal epithelial cells (F,G [arrow]) but no to low levels of 5α-reductase-3 immunostaining were observed in luminal epithelial cells of adjacent benign glands (F,G [arrowhead]). In AS-CaP and CR-CaP, 5α-reductase-3 immunostaining was located in most malignant epithelial cells (I,J,N). 5α-reductase-3 immunostaining was mostly perinuclear when intense (J,N [arrows]. 5α-reductase-3 immunostaining in malignant epithelial cells was confirmed by co-localization of 5α-reductase-3 (brown cytoplasmic stain) and AMACR (red cytoplasmic stain) immunostaining (K). Incubation in the absence of primary antibody provided negative controls (A,E,H,L). Black bars: 30 μM. Images reduced from 200× magnification (columns 1 and 2) or 400× magnification (columns 3 and 4).

References

    1. Labrie F. Intracrinology. Mol Cell Endocrinol. 1991;78(3):C113–118. - PubMed
    1. Russell DW, Wilson JD. Steroid 5 alpha-reductase: two genes/two enzymes. Annu Rev Biochem. 1994;63:25–61. - PubMed
    1. Hawk E, Breslow RA, Graubard BI. Male pattern baldness and clinical prostate cancer in the epidemiologic follow-up of the first National Health and Nutrition Examination Survey. Cancer Epidemiol Biomarkers Prev. 2000;9(5):523–527. - PubMed
    1. Olsen EA, Hordinsky M, Whiting D, Stough D, Hobbs S, Ellis ML, Wilson T, Rittmaster RS. The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: Results of a randomized placebo-controlled study of dutasteride versus finasteride. J Am Acad Dermatol. 2006;55(6):1014–1023. - PubMed
    1. Napalkov P, Maisonneuve P, Boyle P. Worldwide patterns of prevalence and mortality from benign prostatic hyperplasia. Urology. 1995;46(3 Suppl A):41–46. - PubMed

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