Presence of 5α-Reductase isozymes and aromatase in human prostate cancer cells and in benign prostate hyperplastic tissue

✍ Scribed by Negri-Cesi, Paola; Poletti, Angelo; Colciago, Alessandra; Magni, Paolo; Martini, Paolo; Motta, Marcella

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 239 KB
• Volume: 34
• Category: Article
• ISSN: 0270-4137
• DOI: 10.1002/(sici)1097-0045(19980301)34:4<283::aid-pros6>3.0.co;2-i

✦ Synopsis

BACKGROUND. Prostate trophism depends on DHT formed from T by the enzyme 5␣-R. Two 5␣-R isoforms with different biochemical characteristics have been cloned. Also estrogens might contribute to the prostate growth; however, their intraglandular formation by the enzyme aromatase is still debated. The aim of the present study was to verify whether (a) only one or both isoforms of the 5␣-Rs are expressed in the prostate cancer cell line LNCaP and in BPH, or (b) the aromatase is present in these samples. METHODS. The profile of the pH optimum of the 5␣-Rs was evaluated ''in vitro'' in LNCaP cells by the production of labeled 5␣-reduced metabolites either from [ 14 C]-T or [ 14 C]-D4 at pH 3.5-8. The gene expression of the two 5␣-Rs and of the aromatase in LNCaP cells and in BPH specimens was analyzed by RT-PCR combined to Southern blot analysis, using specific sets of oligonucleotides. The tissue localization of 5␣-R1 was analyzed by immunohistochemistry using an anti-5␣-R1 polyclonal antibody. RESULTS. (a) In LNCaP cells, the formation of 5␣-reduced metabolites from the respective precursors increases progressively as a function of pH, being the highest at neutral pH values; (b) the 5␣-R1 isoform is expressed in both LNCaP cells and in BPH, while the 5␣-R2 mRNA is present only in BPH, but not in LNCaP cells; and (c) no aromatase transcripts were observed either in BPH or in LNCaP cells. CONCLUSIONS. A careful examination of the possible differential expression of T-activating enzymes, particularly in prostate cancer, would be of help to choose the appropriate treatment.