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Sustained JNK1 activation is associated with altered histone H3 methylations in human liver cancer.

Authors
Chang-Q; Zhang-Y; Beezhold-KJ; Bhatia-D; Zhao-H; Chen-J; Castranova-V; Shi-X; Chen-F
Source
J Hepatol 2009 Feb; 50(2):323-333
NIOSHTIC No.
20034940
Abstract
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.
Keywords
Laboratory-animals; Liver; Liver-cancer; Liver-cells; Hepatocytes; Hepatotoxins; Genetic-factors; Cell-biology; Cell-differentiation; Cell-function; Cell-metabolism; Cell-morphology; Cellular-reactions; Author Keywords: JNK; HCC; H3K4me3; EZH2; Tumor suppressor; Cancer
Contact
Fei Chen, Health Effects Laboratory Division, National Institute for Occupational Safety and Heath, 1095 Willowdale Road, Morgantown, WV 26505
CODEN
JOHEEC
Publication Date
20090201
Document Type
Journal Article
Email Address
LFD3@cdc.gov
Fiscal Year
2009
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
0168-8278
NIOSH Division
HELD
Priority Area
Manufacturing; Mining
Source Name
Journal of Hepatology
State
WV
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