University of Oulu

17β-Hydroxysteroid dehydrogenases/17-ketosteroid reductases (17HSD/KSRs) in prostate cancer : the role of 17HSD/KSR types 2, 5, and 7 in steroid hormone action and loss of heterozygosity at chromosome region 16q

Saved in:
Author: Härkönen, Päivi1,2,3
Organizations: 1University of Oulu, Faculty of Medicine, Research Center for Molecular Endocrinology
2University of Oulu, Faculty of Medicine, WHO Collaborating Centre for Research on Reproductive Health
3University of Oulu, Biocenter Oulu
Format: ebook
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.1 MB)
Persistent link:
Language: English
Published: 2005
Publish Date: 2005-11-23
Thesis type: Doctoral Dissertation
Defence Note: Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in the Auditorium 8 of Oulu University Hospital, on December 2nd, 2005, at 11 a.m.
Reviewer: Professor Jorma Toppari
Professor Tapio Visakorpi


Prostate cancer is the most frequently diagnosed cancer in men in industrialized countries. Despite the substantial clinical importance of the disease, the mechanisms underlying the development and progression of prostate cancer are poorly understood.

In the present study, fragment analysis of chromosome arm 16q was carried out with the aim of searching for sites of consistent chromosomal deletion, possibly uncovering the location of target genes that become inactivated in prostate carcinogenesis. The highest percentage of loss of heterozygosity (LOH) was found at chromosomal region 16q24.1-q24.2, including the gene for 17β-hydroxysteroid dehydrogenase/17-ketosteroid reductase (17HSD/KSR) type 2, HSD17B2. The data further indicated an association between loss of the most commonly deleted region and clinically aggressive features of the disease. A fragment analysis performed using sequential primary and locally recurrent prostate cancer specimens suggested the location of the genes related to prostate cancer progression to be at 16q24.3 and, further, gave rise to a hypothesis of the potential role of locus HSD17B2 as a prognostic marker for prostate cancer progression. Quantitative real-time polymerase chain reaction (PCR) revealed a decreased HSD17B2 gene copy number in prostate cancer specimens compared to their normal counterparts. A diminished HSD17B2 gene copy number was significantly associated with poor differentiation of the tumor.

The progression of prostate cancer during androgen deprivation is a serious clinical problem, the molecular mechanisms of which largely remain to be clarified. The present data of enzyme activity measurements performed using high-performance liquid chromatography (HPLC) provided evidence of a substantial decrease in oxidative and an increase in reductive 17HSD/KSR activity during the transition of prostate cancer LNCaP cells into an androgen-independent state. Further, the changes detected in the activities largely coincided with the changes in the relative expression levels of genes for the potential 17HSD/KSR isoenzymes; 17HSD/KSR types 2, 5, and 7, as evidenced by relative quantitative reverse transcription PCR (RT-PCR). The data on the expression analysis of mRNA for 17HSD/KSR types 5 and 7 in prostate tissue specimens performed using in situ hybridization showed a moderately low but constitutive level for 17HSD/KSR7 mRNA in tissues of cancerous as well as hyperplastic origin. The expression of mRNA for 17HSD/KSR type 5, instead, varied considerably between different specimens, the highest expressions being strongly associated with aggressive and metastatic prostate cancer. Interestingly, furthermore, the intense expression of 17HSD/KSR5 was significantly associated with the androgen deprivation achieved either surgically or medically.

Since 17HSD/KSRs critically contribute to the control of the bioavailability of active sex steroid hormones locally in the prostate, the variation in intraprostatic 17HSD/KSR activity might be crucially involved in the regulation of the growth and function of the organ.

see all

Series: Acta Universitatis Ouluensis. D, Medica
ISSN-E: 1796-2234
ISBN: 951-42-7937-9
ISBN Print: 951-42-7936-0
Issue: 859
Copyright information: © University of Oulu, 2005. This publication is copyrighted. You may download, display and print it for your own personal use. Commercial use is prohibited.