UMMS Affiliation

Program in Molecular Medicine; Department of Cancer Biology

Publication Date


Document Type



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


Biochemistry | Cancer Biology | Cell Biology | Cellular and Molecular Physiology | Developmental Biology | Molecular Biology


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.


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



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

Link to Article in PubMed

PubMed ID



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