title: The suppressive role and aberrent promoter methylation of BTG3 in the progression of hepatocellular carcinoma.
abstract: BACKGROUND
  BTG3 (B-cell translocation gene 3) has been identified as a tumor suppressor and hypermethylation contributes to its down-regulation in some tumors, but its role in hepatocellular carcinoma (HCC) remain unknown. This study aimed to detect the expression and methylation status of BTG3 in HCC cell lines or tissues, and determine its function in HCC progression.
  
  
  METHODS
  The expression of BTG3 was detected in HCC cell lines and HCC tissue by real-time RT-PCR, Western blot or immunohistochemistry. The promoter methylation status of BTG3 was measured by using methylation-specific PCR in HCC cell lines. A series of assays were performed to evaluate the effect of BTG3 on proliferation, invasion and cell cycle transition in vitro.
  
  
  RESULTS
  BTG3 expression was lower in HCC cell lines than in hepatocyte cell line LO2 (P<0.05). BTG3 was also down-regulated in HCC tissues. Its expression was positively correlated with differentiation and distant metastasis (P<0.05). Patients with lower BTG3 expression had shorter overall survival time (P=0.029). DNA methylation directed repression of BTG3 mRNA expression in HCC cell lines. BTG3 suppressed proliferation, invasion and induces G1/S cycle arrest of HCC cells in vitro.
  
  
  CONCLUSIONS
  Down-regulation of BTG3 due to the promoter hypermethylation is closely associated with proliferation, invasion and cell cycle arrest of HCC cells. It may be a novel prognostic biomarker for HCC patients.
authors.affiliation: Department of Pathology, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China ; Department of General Surgery, Nanchong Central Hospital, Nanchong City, Sichuan Province, People's Republic of China.
authors.forename: Zhenbing
authors.initials: Z
authors.lastname: Lv
authors.forename: Huichun
authors.initials: H
authors.lastname: Zou
authors.forename: Kaiwen
authors.initials: K
authors.lastname: Peng
authors.forename: Jianmei
authors.initials: J
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.forename: Yuling
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ren
authors.forename: Feifei
authors.initials: F
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Chang
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D047368:Tumor Burden
chemical_list: C424522:BTG3 protein, human; D018797:Cell Cycle Proteins; D011506:Proteins