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Presence of 5α‐Reductase isozymes and aromatase in human prostate cancer cells and in benign prostate hyperplastic tissue
Author(s) -
NegriCesi Paola,
Poletti Angelo,
Colciago Alessandra,
Magni Paolo,
Martini Paolo,
Motta Marcella
Publication year - 1998
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(19980301)34:4<283::aid-pros6>3.0.co;2-i
Subject(s) - lncap , aromatase , prostate , prostate cancer , endocrinology , isozyme , medicine , gene isoform , immunohistochemistry , biology , cancer research , chemistry , cancer , enzyme , breast cancer , biochemistry , gene
BACKGROUND Prostate trophism depends on DHT formed from T by the enzyme 5α‐R. Two 5α‐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 5α‐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 5α‐Rs was evaluated “in vitro” in LNCaP cells by the production of labeled 5α‐reduced metabolites either from [ 14 C]‐T or [ 14 C]‐D4 at pH 3.5–8. The gene expression of the two 5α‐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 5α‐R1 was analyzed by immunohistochemistry using an anti‐5α‐R1 polyclonal antibody. RESULTS (a) In LNCaP cells, the formation of 5α‐reduced metabolites from the respective precursors increases progressively as a function of pH, being the highest at neutral pH values; (b) the 5α‐R1 isoform is expressed in both LNCaP cells and in BPH, while the 5α‐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. Prostate 34:283–291, 1998. © 1998 Wiley‐Liss, Inc.