title: Methylation-mediated silencing of SOCS-1 gene in hepatocellular carcinoma derived from cirrhosis.
abstract: OBJECTIVE
  Suppressor of cytokine signaling-1 (SOCS-1) is a negative regulator of Janus kinase and signal transducer and activation of transcription pathway. Recently, it was demonstrated that SOCS-1 gene was silenced frequently by methylation of CpG island in human hepatocellular carcinoma (HCC). We examined the methylation-mediated silencing of SOCS-1 in tumors of HCC patients.
  
  
  METHODS
  Fifty patients with HCC were investigated in this study. We examined the methylation status of the SOCS-1 promoter region by methylation-specific PCR and then confirmed the methylation-mediated silencing of SOCS-1 by Northern blot analysis. Furthermore, this methylation status was compared with clinicopathological findings.
  
  
  RESULTS
  Aberrant methylation of the SOCS-1 gene was detected in 30 of 50 (60%) HCC specimens. No corresponding nontumorous liver tissues showed SOCS-1 methylation. Subsequent Northern analysis proved that methylation of the SOCS-1 promoter inactivated translation and diminished expression of SOCS-1 mRNA. We then analyzed the correlation between the clinicopathological data and SOCS-1 aberrant methylation and found that HCC derived from liver cirrhosis had a significant relationship with SOCS-1 methylation (P = 0.0207).
  
  
  CONCLUSIONS
  SOCS-1 may be a novel tumor suppressor, and its aberrant methylation may be a key event for HCC transformation of cirrhotic nodules.
authors: Second Department of Surgery, Nagoya University School of Medicine, Nagoya, Japan.
authors: Osamu
authors: O
authors: Okochi
authors: Kenji
authors: K
authors: Hibi
authors: Mitsuru
authors: M
authors: Sakai
authors: Soichiro
authors: S
authors: Inoue
authors: Shin
authors: S
authors: Takeda
authors: Tetsuya
authors: T
authors: Kaneko
authors: Akimasa
authors: A
authors: Nakao
mesh_terms: D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology*; D008297:Male; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins