title: Sustained JNK1 activation is associated with altered histone H3 methylations in human liver cancer.
abstract: OBJECTIVE
  Aberrant c-Jun N-terminal kinase (JNK) activation has been linked to hepatocellular carcinoma (HCC) in mouse models. It remains unclear whether JNK activation plays an important role in human HCC and, if so, how JNK signaling contributes to the initiation or progression of HCC.
  
  
  METHODS
  The JNK activation, global gene expression, and the status of histone H3 methylations were measured in 31 primary human hepatocellular carcinoma (HCC) samples paired with the adjacent non-cancerous (ANC) tissues.
  
  
  RESULTS
  Enhanced JNK1 activation was noted in 17 out of 31 HCC samples (55%) relative to the corresponding ANC tissues, whereas JNK2 activation was roughly equal between HCC and ANC tissues. This enhancement in JNK1 activation is associated with an increased tumor size and a lack of encapsulation of the tumors. In addition, an association of JNK1 activation with the histone H3 lysines 4 and 9 tri-methylation was observed in the HCC tissues, which leads to an elevated expression of genes regulating cell growth and a decreased expression of the genes for cell differentiation and the p450 family members in HCC.
  
  
  CONCLUSIONS
  These results, thus, suggest that JNK1 plays important roles in the development of human HCC partially through the epigenetic mechanisms.
authors.affiliation: Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Chang
authors.forename: Yadong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Beezhold
authors.forename: Deepak
authors.initials: D
authors.lastname: Bhatia
authors.forename: Hongwen
authors.initials: H
authors.lastname: Zhao
authors.forename: Jianguo
authors.initials: J
authors.lastname: Chen
authors.forename: Vince
authors.initials: V
authors.lastname: Castranova
authors.forename: Xianglin
authors.initials: X
authors.lastname: Shi
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics; D000071221:Enhancer of Zeste Homolog 2 Protein; D004789:Enzyme Activation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008745:Methylation; D008875:Middle Aged; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D048055:Mitogen-Activated Protein Kinase 8