PMID- 15294155 OWN - NLM STAT- MEDLINE DCOM- 20040901 LR - 20220410 IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 118 IP - 3 DP - 2004 Aug 6 TI - IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. PG - 285-96 AB - 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. FAU - Greten, Florian R AU - Greten FR AD - Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla 92093, USA. FAU - Eckmann, Lars AU - Eckmann L FAU - Greten, Tim F AU - Greten TF FAU - Park, Jin Mo AU - Park JM FAU - Li, Zhi-Wei AU - Li ZW FAU - Egan, Laurence J AU - Egan LJ FAU - Kagnoff, Martin F AU - Kagnoff MF FAU - Karin, Michael AU - Karin M LA - eng GR - AI43477/AI/NIAID NIH HHS/United States GR - AI56075/AI/NIAID NIH HHS/United States GR - DK35108/DK/NIDDK NIH HHS/United States GR - ES10337/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cell JT - Cell JID - 0413066 RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.10 (Chuk protein, mouse) RN - EC 2.7.11.10 (I-kappa B Kinase) RN - EC 2.7.11.10 (Ikbkb protein, mouse) RN - EC 2.7.11.10 (Ikbke protein, mouse) SB - IM CIN - Cell. 2004 Sep 17;118(6):671-4. PMID: 15369667 MH - Animals MH - Apoptosis/physiology MH - Colitis/*metabolism MH - Colonic Neoplasms/etiology/*metabolism MH - Enterocytes/enzymology/metabolism MH - I-kappa B Kinase MH - Inflammation/enzymology/*metabolism MH - Mice MH - Myeloid Cells/physiology MH - Protein Serine-Threonine Kinases/deficiency/*metabolism EDAT- 2004/08/06 05:00 MHDA- 2004/09/02 05:00 CRDT- 2004/08/06 05:00 PHST- 2003/11/21 00:00 [received] PHST- 2004/06/11 00:00 [revised] PHST- 2004/06/18 00:00 [accepted] PHST- 2004/08/06 05:00 [pubmed] PHST- 2004/09/02 05:00 [medline] PHST- 2004/08/06 05:00 [entrez] AID - S0092867404006713 [pii] AID - 10.1016/j.cell.2004.07.013 [doi] PST - ppublish SO - Cell. 2004 Aug 6;118(3):285-96. doi: 10.1016/j.cell.2004.07.013.