title: Reduced levels of 5-α reductase 2 in adult prostate tissue and implications for BPH therapy.
abstract: BACKGROUND
  5-α reductase 2 (5-AR 2) is a key enzyme that is responsible of proper development of prostate tissue. Inhibition of 5-AR 2 has proven to be efficacious for management of urinary symptoms secondary benign prostatic hyperplasia (BPH). However, some patients are resistant to the therapeutic effects of 5-AR 2 inhibitor. We wished to determine why some benign non-cancerous adult human prostates do not express 5-AR 2, and hypothesized that methylation of 5-AR 2 promoter region correlated with low expression of 5-AR 2 protein.
  
  
  METHODS
  The transition zone of 42 human prostate tissues after radical prostatectomy was used for evaluation. Initially, 21 paraffin embedded samples were used to assess immunoreactivity to 5-AR 2 antibody in non-cancerous BPH samples. In the next 21 samples, fresh frozen prostate transition zone samples without cancer were assessed for immunoreactivity and methylation of the 5-AR 2 promoter using methyl-specific PCR.
  
  
  RESULTS
  We show that 6/21 (29%) of benign human prostate samples did not express the 5-AR 2 protein. Moreover, the promoter region of 5-AR 2 contains a CpG island that is methylated in benign prostate epithelial cells in culture and also in 39% (7/18) human prostate tissues. We show a strong correlation between methylation of the 5-AR 2 promoter region and absence of 5-AR 2 protein expression (P = 0.0025, Fisher's exact test).
  
  
  CONCLUSIONS
  Methylation of 5-AR 2 promoter may account for low or absent expression of 5-AR 2 in some human adult prostate tissues.
authors.affiliation: Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Yinong
authors.initials: Y
authors.lastname: Niu
authors.forename: Rongbin
authors.initials: R
authors.lastname: Ge
authors.forename: Libing
authors.initials: L
authors.lastname: Hu
authors.forename: Christian
authors.initials: C
authors.lastname: Diaz
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Wang
authors.forename: Chin-Lee
authors.initials: CL
authors.lastname: Wu
authors.forename: Aria F
authors.initials: AF
authors.lastname: Olumi
mesh_terms: D000368:Aged; D002461:Cell Line, Transformed; D042944:Cholestenone 5 alpha-Reductase / Q000235:genetics / Q000378:metabolism*; D018899:CpG Islands; D019175:DNA Methylation; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000201:enzymology*; D011470:Prostatic Hyperplasia / Q000201:enzymology* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007527:Isoenzymes; D042944:Cholestenone 5 alpha-Reductase