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2 immune-system proteins linked to colitis-associated cancer
Date:2/2/2009

Recent research from the laboratory of Michael Karin, PhD, at the University of California, San Diego School of Medicine the first researcher to demonstrate a molecular link between inflammation and cancer has identified two potential targets for the prevention and treatment of colitis-associated cancer (CAC), the most serious complication of inflammatory bowel disease.

Karin, Distinguished Professor of Pharmacology and Pathology and member of the Moores UCSD Cancer Center, and his team used genetic tools to demonstrate in mice that a cytokine called Interleukin 6 (IL-6), is an important regulator of tumor production during CAC development, and that its molecular effects are largely mediated by the transcription factor STAT3 in cancer cells. Their latest study which is also the first to establish the cancer-promoting function of STAT3 in a validated mouse model of human cancer will be published in the February 3 on-line edition of the journal Cancer Cell.

Recurrent inflammation and chronic infections contribute to a large number of different cancers including CAC which occurs in people suffering from chronic colitis, a common inflammatory bowel disease, putting them at very high risk for cancer. Cytokines small proteins released by immune-system cells have been suggested to drive early tumor growth by stimulating the growth and survival of pre-malignant cells.

In previous work, Karin's team showed that activation of a pro-inflammatory protein called NF-kB stimulates the proliferation of premalignant epithelial cells in CAC, giving rise to malignant growths in the colon. Interestingly, NF-kB in colonic epithelial cells promotes the development of cancer, not through inflammation, but through inhibition of apoptosis or cell death. On the other hand, NF-kB in the immune cells promotes cancer by enhancing inflammation, mostly by controlling the expression of pro-inflammatory cytokine expression. One of these cytokines w
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Contact: Debra Kain
ddkain@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

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