title: Epigenetic down regulation of RASSF10 and its possible clinical implication in prostate carcinoma.
abstract: BACKGROUND
  Ras association domain family (RASSF) comprises several tumor suppressor genes, which are often epigenetically inactivated in human tumors. Here, we aim to analyze the relevance of the recently identified member RASSF10 in prostate carcinogenesis.
  
  
  METHODS
  RASSF10 promoter methylation and mRNA expression were investigated by bisulfite-pyrosequencing and qRT-PCR, respectively, in prostate carcinoma (PCa) cell lines (LNCaP, 22Rv1, DU-145) and in 83 primary PCa and 53 primary benign prostatic hyperplasia (BPH) tissues obtained after radical prostatectomy. Histological localization of RASSF10 was done by in situ hybridization. To prove the epigenetic nature of RASSF10 down regulation, PCa cell lines were treated with 5-aza-2-deoxycytidine and trichostatin A. Potential function of RASSF10 was analyzed in LNCaP by colony formation and apoptosis assays.
  
  
  RESULTS
  RASSF10 mRNA was localized to cells of the basal layer of the prostatic gland. Absence (LNCaP) and decrease (22Rv1, DU-145) of RASSF10 expression was associated with promoter methylation and could be restored by demethylating agents. A link between RASSF10 mRNA reduction and promoter methylation was also detected in primary prostate tissues (P = 0.006), where PCa showed more frequently reduced RASSF10 levels when compared with BPH (33.7% vs. 13.2%, P = 0.009). RASSF10 methylation could be further associated with advanced tumor stage and advanced age (P-values < 0.05). Our preliminary functional assays revealed the ability of RASSF10 to inhibit colony formation (P = 0.018) and to increase apoptosis (P = 0.035).
  
  
  CONCLUSIONS
  This is the first study, which demonstrates the frequent epigenetic inactivation of RASSF10 in PCa and its implication in clinical symptoms of PCa.
authors.affiliation: Department of Urology, Pediatric Urology and Andrology, Justus Liebig University Giessen, Giessen, Germany.
authors.forename: Temuujin
authors.initials: T
authors.lastname: Dansranjavin
authors.forename: Florian
authors.initials: F
authors.lastname: Wagenlehner
authors.forename: Stefan
authors.initials: S
authors.lastname: Gattenloehner
authors.forename: Klaus
authors.initials: K
authors.lastname: Steger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weidner
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dammann
authors.forename: Undraga
authors.initials: U
authors.lastname: Schagdarsurengin
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics; D015536:Down-Regulation; D057890:Epigenomics / Q000379:methods; D005434:Flow Cytometry; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics*; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C548440:RASSF10 protein, human; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins