MOLECULAR EXPRESSION OF 17-BETA-HYDROXYSTEROID DEHYDROGENASE TYPES INRELATION TO THEIR ACTIVITY IN INTACT HUMAN PROSTATE-CANCER CELLS

In the present study we have inspected estrogen metabolism in cultured human prostate cancer cells (LNCaP, DU145, PC3), in relation to the e xpression of mRNAs for different 17 beta hydroxysteroid dehydrogenase (17 beta HSD) enzymes (from 1 to 4). Using an intact cell analysis, we have compared precursor degradation and product formation after incub ation of cells with physiological amounts of radioactive E-2 or estron e (E-1) for 24-72 h and subsequent reverse-phase high performance liqu id chromatography analysis. The LNCaP and DU145 cells only partly conv erted E-2 to E-1 (26 and 13%, at 72 h, respectively), giving rise to a n appreciable production of E, from E, (nearly 20% in all cases). Conv ersely, PC3 cells revealed a massive E, oxidation to E, (up to 90%, by 72 h) and a scant formation of E-2 ( < 2%) from E-1. In addition, an appreciable formation of 16 alpha OHE1 was seen in either PC3 (11%) or DU145 (5%) cells, respectively using E-2 or E-1 as precursor. All thr ee cell lines exhibited marked amounts of 17 beta HSD4 mRNA species, w hilst even greater amounts of 17 beta HSD2 transcript were found in PC 3 cells only. No mRNA for either 17 beta HSD1 or 17 beta HSD3 could be detected in any cell line. The present evidence indicates that pathwa ys of estrogen metabolism are distinctly governed in prostate cancer c ells depending on their endocrine status, being associated with a diff erential expression of mRNA for different 17 beta HSD enzymes. (C) 199 7 Elsevier Science Ireland Ltd.