title: Tumor suppressor function of PGP9.5 is associated with epigenetic regulation in prostate cancer--novel predictor of biochemical recurrence after radical surgery.
abstract: BACKGROUND
  The expression level of protein G product 9.5 (PGP9.5) is downregulated because of promoter CpG hypermethylation in several tumors. We speculated that impaired regulation of PGP9.5 through epigenetic pathways is associated with the pathogenesis of prostate cancer.
  
  
  METHODS
  CpG methylation of the PGP9.5 gene was analyzed in cultured prostate cancer cell lines, 226 localized prostate cancer samples from radical prostatectomy cases, and 80 benign prostate hyperplasia (BPH) tissues.
  
  
  RESULTS
  Following 5-aza-2'-deoxycytidune treatment, increased PGP9.5 mRNA transcript expression was found in the LNCaP and PC3 cell lines. With bisulfite DNA sequencing, partial methylation of the PGP9.5 promoter was shown in LNCaP whereas complete methylation was found in PC3 cells. After transfection of PGP9.5 siRNA, cell viability was significantly accelerated in LNCaP but not in PC3 cells as compared with control siRNA transfection. Promoter methylation of PGP9.5 was extremely low in only one of 80 BPH tissues, whereas it was found in 37 of 226 prostate cancer tissues. Expression of the mRNA transcript of PGP9.5 was significantly lower in methylation (+) than methylation (-) prostate cancer tissues. Multivariate analysis of biochemical recurrence (BCR) after an radical prostatectomy revealed pT category and PGP9.5 methylation as prognostically relevant. Further stratification with the pT category in addition to methylation status identified a stepwise reduction of BCR-free probability.
  
  
  CONCLUSIONS
  This is the first clinical and comprehensive study of inactivation of the PGP9.5 gene via epigenetic pathways in primary prostate cancer.
  
  
  CONCLUSIONS
  CpG methylation of PGP9.5 in primary prostate cancer might become useful as a molecular marker for early clinical prediction of BCR after radical prostatectomy.
authors.affiliation: Department of Urology, Shimane University School of Medicine, Izumo, Shimane, Japan.
authors.forename: Yozo
authors.initials: Y
authors.lastname: Mitsui
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shiina
authors.forename: Miho
authors.initials: M
authors.lastname: Hiraki
authors.forename: Naoko
authors.initials: N
authors.lastname: Arichi
authors.forename: Takeo
authors.initials: T
authors.lastname: Hiraoka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sumura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Honda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yasumoto
authors.forename: Mikio
authors.initials: M
authors.lastname: Igawa
mesh_terms: D000368:Aged; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D057890:Epigenomics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D011401:Promoter Regions, Genetic; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D043222:Ubiquitin Thiolesterase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D034741:RNA, Small Interfering; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase