The role of JNK in the development of hepatocellular carcinoma
- 1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
- 2Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA;
- 3Howard Hughes Medical Institute, Worcester, Massachusetts 01605, USA
Abstract
The cJun NH2-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.
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Footnotes
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↵4 Corresponding author.
E-MAIL roger.davis{at}umassmed.edu; FAX (508) 856-3210.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1989311.
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Supplemental material is available for this article.
- Received September 3, 2010.
- Accepted February 2, 2011.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press
Freely available online through the Genes & Development Open Access option.