UMMS Affiliation
Program in Molecular Medicine; Department of Cancer Biology
Publication Date
2011-03-15
Document Type
Article
Subjects
Animals; Carcinoma, Hepatocellular; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Cytokines; *Hepatocytes; Interleukin-6; Liver; Liver Neoplasms; Liver Regeneration; Mice; Mice, Inbred C57BL; *Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinase 9; Proto-Oncogene Proteins c-myc; Signal Transduction; Tumor Cells, Cultured
Disciplines
Biochemistry | Cancer Biology | Cell Biology | Cellular and Molecular Physiology | Developmental Biology | Molecular Biology
Abstract
The cJun NH(2)-terminal kinase (JNK) signal transduction pathway has been implicated in the growth of carcinogen-induced hepatocellular carcinoma. However, the mechanism that accounts for JNK-regulated tumor growth is unclear. Here we demonstrate that compound deficiency of the two ubiquitously expressed JNK isoforms (JNK1 and JNK2) in hepatocytes does not prevent hepatocellular carcinoma development. Indeed, JNK deficiency in hepatocytes increased the tumor burden. In contrast, compound JNK deficiency in hepatocytes and nonparenchymal cells reduced both hepatic inflammation and tumorigenesis. These data indicate that JNK plays a dual role in the development of hepatocellular carcinoma. JNK promotes an inflammatory hepatic environment that supports tumor development, but also functions in hepatocytes to reduce tumor development.
Keywords
JNK, partial hepatectomy, hepatocellular carcinoma
Rights and Permissions
Copyright © 2011 by Cold Spring Harbor Laboratory Press. Freely available online through the Genes and Development Open Access option.
DOI of Published Version
10.1101/gad.1989311
Source
Genes Dev. 2011 Mar 15;25(6):634-45. doi: 10.1101/gad.1989311. Link to article on publisher's site
Journal/Book/Conference Title
Genes and development
Related Resources
PubMed ID
21406557
Repository Citation
Das, Madhumita; Garlick, David S.; Greiner, Dale; and Davis, Roger J., "The role of JNK in the development of hepatocellular carcinoma" (2011). Davis Lab Publications. 32.
https://escholarship.umassmed.edu/davis/32
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