Literature DB >> 15538746

Differential alterations in 5alpha-reductase type 1 and type 2 levels during development and progression of prostate cancer.

Lynn N Thomas1, C B Lazier, R Gupta, R W Norman, D A Troyer, S P O'Brien, R S Rittmaster.   

Abstract

BACKGROUND: In the prostate, conversion of testosterone to dihydrotestosterone (DHT), by the enzymes 5alpha-reductase types 1 and 2 (5alphaR1, 5alphaR2) is required for normal growth and probably also for development of prostate cancer (PCa). Finasteride, a 5alphaR2 inhibitor, was shown to reduce the prevalence of PCa in the Prostate Cancer Prevention Trial. However, inhibition of both 5alphaR isoenzymes causes a greater decrease in serum DHT. The aim of this study was to assess differential expression of these enzymes at various stages of PCa development.
METHODS: Immunostaining for 5alphaR1 and 5alphaR2, using specific, well-validated antibodies, was evaluated in 26 benign prostatic hyperplasia (BPH) (16 for 5alphaR2), 53 primary PCa (21 for 5alphaR2), 18 prostatic intraepithelial neoplasia (PIN), 12 primary PCa treated with neoadjuvant androgen ablation, 15 locally recurrent PCa specimens, and 18 PCa metastases.
RESULTS: The mean area of moderate plus high intensity staining for 5alphaR1 increased from 4.8 +/- 2.8% of total epithelial area in BPH, to 18.9 +/- 5.7% in PIN, 17.0 +/- 3.2% in primary cancer, 38.0 +/- 7.3% in recurrent cancer, and 55.8 +/- 8.5% in PCa metastases. The mean staining area for 5alphaR2 decreased from 58.8 +/- 7.2% in BPH, to 21.1 +/- 5.5% in PIN and 34.8 +/- 6.7% in primary PCa. Staining for 5alphaR2 was increased in recurrent cancer and PCa metastases compared to primary PCa, at 58.7 +/- 5.2% and 69.2 +/- 8.7%, respectively.
CONCLUSIONS: 5alphaR1 immunostaining is increased and 5alphaR2 immunostaining is decreased during development of PCa. In addition, there is increased expression of both 5alphaR isozymes in recurrent and metastatic cancers, suggesting that both isozymes may be important in the development and progression of PCa. (c) 2004 Wiley-Liss, Inc.

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Year:  2005        PMID: 15538746     DOI: 10.1002/pros.20188

Source DB:  PubMed          Journal:  Prostate        ISSN: 0270-4137            Impact factor:   4.104


  38 in total

1.  Dutasteride and prostate cancer risk.

Authors:  Haim Matzkin
Journal:  Curr Urol Rep       Date:  2010-09       Impact factor: 3.092

2.  Expression in Escherichia Coli, Purification, and Functional Reconstitution of Human Steroid 5α-Reductases.

Authors:  Hwei-Ming Peng; Juan Valentín-Goyco; Sang-Choul Im; Bing Han; Jiayan Liu; Jie Qiao; Richard J Auchus
Journal:  Endocrinology       Date:  2020-08-01       Impact factor: 4.736

3.  Intraethnic variation in steroid-5-alpha-reductase polymorphismsin prostate cancer patients: a potential factor implicated in 5-alpha-reductase inhibitor treatment.

Authors:  Luis Alberto Henríquez-Hernández; Almudena Valenciano; Palmira Foro-Arnalot; María Jesús Álvarez-Cubero; José Manuel Cozar; José Francisco Suárez-Novo; Manel Castells-Esteve; Pablo Fernández-Gonzalo; Belén De-Paula-Carranza; Montse Ferrer; Ferrán Guedea; Gemma Sancho-Pardo; Jordi Craven-Bartle; María José Ortiz-Gordillo; Patricia Cabrera-Roldán; Estefanía Herrera-Ramos; Carlos Rodríguez-Gallego; Pedro C Lara
Journal:  J Genet       Date:  2015-06       Impact factor: 1.166

4.  5-alpha reductase inhibitors in patients on active surveillance: do the benefits outweigh the risk?

Authors:  Ghazi Al Edwan; Neil Fleshner
Journal:  Curr Urol Rep       Date:  2013-06       Impact factor: 3.092

5.  Correlation between 5-α reductase type 2 protein expression and methylation of 5-α reductase type 2 promotor gene of benign prostatic hyperplasia.

Authors:  Pil Moon Kang; Young Jin Kim; Won Tae Seo; Su Hwan Kang; Taek Sang Kim; Bong Kwon Chun; Won Ik Seo; Jee-Yeong Jeong; Jae Il Chung
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Review 6.  Androgen action in prostate cancer.

Authors:  Sujit Basu; Donald J Tindall
Journal:  Horm Cancer       Date:  2010-10       Impact factor: 3.869

7.  SRD5A2 and HSD3B2 polymorphisms are associated with prostate cancer risk and aggressiveness.

Authors:  Christine Neslund-Dudas; Cathryn H Bock; Kristin Monaghan; Nora L Nock; James J Yang; Andrew Rundle; Deliang Tang; Benjamin A Rybicki
Journal:  Prostate       Date:  2007-11-01       Impact factor: 4.104

Review 8.  The rationale for inhibiting 5alpha-reductase isoenzymes in the prevention and treatment of prostate cancer.

Authors:  Donald J Tindall; Roger S Rittmaster
Journal:  J Urol       Date:  2008-02-20       Impact factor: 7.450

Review 9.  The basic biochemistry and molecular events of hormone therapy.

Authors:  Elahe A Mostaghel; Robert B Montgomery; Daniel W Lin
Journal:  Curr Urol Rep       Date:  2007-05       Impact factor: 3.092

Review 10.  Current status of 5alpha-reductase inhibitors in the management of lower urinary tract symptoms and BPH.

Authors:  Stavros Gravas; Matthias Oelke
Journal:  World J Urol       Date:  2009-12-03       Impact factor: 4.226

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