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Expression of different 17β-hydroxysteroid dehydrogenase types and their activities in human prostate cancer cells.
Endocrinology 138, 4876-4882 (1997)
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The 17β-hydroxysteroid dehydrogenase (17 βHSD) enzyme system governs important redox reactions at the C17 position of steroid hormones. Different 17 βHSD types (no. 1-4) have been identified to date in peripheral human tissues, such as placenta, testis, and breast. However, there is little information on their expression and activity in either normal or malignant prostate. In the present work, we have inspected pathways of 17 β-oxidation of either androgen or estrogen in human prostate cancer cells (LNCaP, DU145, and PC3) in relation to the expression of messenger RNAs (mRNAs) for 17 βHSD types 1-4. These cell systems feature distinct steroid receptor status and response to hormones. We report here that high expression levels of 17 βHSD4 were consistently observed in all three cell lines, whereas even greater amounts of 17 βHSD2 mRNA were detected solely in PC3 cells. Neither 17 βHSD1 nor 17 βHSD3 mRNAs could be detected in any cell line. From a metabolic standpoint, intact cell analysis showed a much lower extent of 17 β-oxidation of both androgen [testosterone (T)] and estrogen [estradiol (E2)] in LNCaP and DU145 cells compared to PC3 cells, where a greater precursor degradation and higher formation rates of oxidized derivatives (respectively, androstenedione and estrone) were observed. Using subcellular fractionation, we have been able to differentiate among 17 βHSD types 1-4 on the basis of their distinct substrate specificities and subcellular localization. This latter approach gave rise to equivalent results. PC3 cells, in fact, displayed a high level of microsomal activity with a low E2/T activity ratio and approximately equal apparent K(m) values for E2and T, suggesting the presence of 17 β3HSD2. Dehydrogenase specific activity with both E2and T was also detected, although at lower levels, in LNCaP and DU145 cells. No evidence for reductase activity could be obtained in either the soluble or microsomal fraction of any cell line. As comparable expression levels of 17 βHSD4 were seen in the three cell lines, 17 βHSD2 is a likely candidate to account for the predominant oxidative activity in PC3 cells, whereas 17 βHSD4 may account for the lower extent of E2oxidation seen in both LNCaP and DU145 cells. This is the first report on the expression of four different 17 βHSD types in human prostate cancer cells. It ought to be emphasized that for the first time, analysis of different 17 βHSD activities in either intact or fractionated cells harmonizes with the expression of relevant mRNAs species.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0013-7227
Quellenangaben Band: 138, Heft: 11, Seiten: 4876-4882
Verlag Endocrine Society
Verlagsort Chevy Chase, Md.
Begutachtungsstatus Peer reviewed
Institut(e) Molekulare Endokrinologie und Metabolismus (MEM)