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UCSD researchers are first to demonstrate molecular link between inflammation and cancer

First evidence of the molecular link between inflammation and cancer has been shown by researchers at the University of California, San Diego (UCSD) School of Medicine. Featured as the cover article in the August 6, 2004 issue of the journal Cell, the study also demonstrated that inactivation of a gene involved in the inflammatory process can dramatically reduce tumor development in mice with a gastrointestinal form of cancer.

The investigators found that a gene called I-kappa-B kinase (IKK beta), a pro-inflammatory gene, acts differently in two cell types to cause cancer. When IKK beta was deleted, the cancer incidence and tumor growth in mice was decreased by nearly 80 percent.

IKK beta is required for activation of a protein called nuclear factor kappa B (NF-kB), that acts as a master switch to turn on inflammation in response to bacterial or viral infections. In epithelial cells, NF-kB promotes the development of cancer not through inflammation, but through inhibition of a cell-killing process called apoptosis. In myeloid cells, NF-kB causes the expression of pro-inflammatory molecules that stimulate the division of genetically altered epithelial cells and thereby increase tumor size.

Because recurrent inflammation and chronic infections contribute to a large number of different cancers, the researchers chose one of these cancers colitis associated cancer (CAC) as their model for study. CAC occurs in people suffering from chronic colitis, which puts them at very high risk for cancer.

"We've shown how tumors arise from chronic infection and inflammation that act together with chemical carcinogens," said the study's senior author, Michael Karin, Ph.D., UCSD professor of pharmacology, American Cancer Society Research Professor, and a member of the Rebecca and John Moores UCSD Cancer Center.

"In response to chronic infection, the interplay between immune cells and the epithelial cells of the intestinal tra
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Contact: Sue Pondrom
spondrom@ucsd.edu
619-543-6163
University of California - San Diego
5-Aug-2004


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