Cell
Volume 118, Issue 3, 6 August 2004, Pages 285-296
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Article
IKKβ Links Inflammation and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer

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Abstract

A link between inflammation and cancer has long been suspected, but its molecular nature remained ill defined. A key player in inflammation is transcription factor NF-κB whose activity is triggered in response to infectious agents and proinflammatory cytokines via the IκB kinase (IKK) complex. Using a colitis-associated cancer model, we show that although deletion of IKKβ in intestinal epithelial cells does not decrease inflammation, it leads to a dramatic decrease in tumor incidence without affecting tumor size. This is linked to increased epithelial apoptosis during tumor promotion. Deleting IKKβ in myeloid cells, however, results in a significant decrease in tumor size. This deletion diminishes expression of proinflammatory cytokines that may serve as tumor growth factors, without affecting apoptosis. Thus, specific inactivation of the IKK/NF-κB pathway in two different cell types can attenuate formation of inflammation-associated tumors. In addition to suppressing apoptosis in advanced tumors, IKKβ may link inflammation to cancer.

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