Loss of Liver NF-κB Activity Boosts Chemical Carcinogenesis

Michael Karin, Ph.D.
School of Medicine, University of California at San Diego
R37ES04151, R01ES06376, and P42ES10337

New research findings from the University of California at San Diego shed light on the link between chronic inflammation and development of cancer. Michael Karin and colleagues have been studying a transcription factor known as NF-κB; previous research has identified it as an important component in the inflammation/cancer connection. Using a transgenic mouse strain lacking a enzyme that activates NF-κB, they have determined that chemically-induced liver cancer occurs through prolonged activation of another enzyme known as c-Jun N-terminal kinase 1 (JNK1).

The most common form of liver cancer is hepatocellular carcinoma (HCC), which is the third leading cause of cancer deaths worldwide. HCC has been linked to chronic infections of hepatitis B and C virus. Although HCC is relatively rare in the U.S., its incidence is growing rapidly due to the increase in cases of hepatitis C. HCC has also been linked to exposure to genotoxic and cytotoxic factors such as high alcohol consumption and aflatoxin, which cause chronic inflammation and liver injury.

Karin and colleagues point out that ”the exact cellular and molecular mechanism through which JNK1 promotes tumor growth, progression, and angiogenesis requires further investigation.” However they conclude that despite the uncertainties in the mechanism, these results "strongly suggest that JNK1 is an important target for the development of chemopreventive and therapeutic measures for reducing the emergence of HCC in the context of chronic liver injury and slowing the progression of preexisting tumors."

Citation: Sakurai T, Maeda S, Chang L, Karin M. Loss of hepatic NF-κB activity enhances chemical hepatocarcinogenesis through sustained c-Jun N-terminal kinase 1 activation. Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10544-51.