Sustained JNK1 Activation Is Associated with Altered Histone H3 Methylations in Human Liver Cancer

Details

• Personal Author:
  Beezhold KJ ; Bhatia D ; Castranova, Vincent ; Chang Q ; Chen F ; Chen J ; Shi X ; Zhang Y ; Zhao H
• Description:
  Background/Aims: 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. [Description provided by NIOSH]
• Subjects:
  Genetics Laboratories Liver Neoplasms Occupational Health Safety
• Keywords:
  Author Keywords: JNK Cancer Cell-biology Cell-differentiation Cell-function Cell-metabolism Cell-morphology Cellular-reactions EZH2 Genetic-factors H3K4me3 HCC Hepatocytes Hepatotoxins Laboratory-animals Liver-cancer Liver-cells Tumor Suppressor

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• ISSN:
  0168-8278
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  323-333
• Volume:
  50
• Issue:
  2
• NIOSHTIC Number:
  nn:20034940
• Citation:
  J Hepatol 2009 Feb; 50(2):323-333
• Contact Point Address:
  Fei Chen, Health Effects Laboratory Division, National Institute for Occupational Safety and Heath, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  LFD3@cdc.gov
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Manufacturing ; Mining
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Hepatology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8bacdb89cab7cf1c8c9b217a42b773b6e0d56c459174b3873ccb56f993da025e4ac8917099fb45bfab0da66306828444693b4daf328f8cc83d59caea746610e3
• Download URL:
  https://stacks.cdc.gov/view/cdc/186955/cdc_186955_DS1.pdf
• File Type:
  [PDF - 360.02 KB ]