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Cell. 2004 Aug 6;118(3):285-96.

IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer.

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1
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla 92093, USA.

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-kappaB whose activity is triggered in response to infectious agents and proinflammatory cytokines via the IkappaB kinase (IKK) complex. Using a colitis-associated cancer model, we show that although deletion of IKKbeta 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 IKKbeta 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-kappaB pathway in two different cell types can attenuate formation of inflammation-associated tumors. In addition to suppressing apoptosis in advanced tumors, IKKbeta may link inflammation to cancer.

PMID:
15294155
DOI:
10.1016/j.cell.2004.07.013
[Indexed for MEDLINE]
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