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Open Access Green as soon as Postprint is submitted to ZB.
Transcription factor NFATc2 controls the emergence of colon cancer associated with IL-6-dependent colitis.
Cancer Res. 72, 4340-4350 (2012)
NFAT transcription factors control T-cell activation and function. Specifically, the transcription factor NFATc2 affects the regulation of cell differentiation and growth and plays a critical role in the development of colonic inflammation. Here, we used an experimental model of colitis-associated colorectal carcinoma to investigate the contribution of NFATc2 to the promotion of colonic tumors. Compared with wild-type animals that readily presented with multiple colon tumors, NFATc2-deficient mice were protected from tumor development. This observed decrease in colonic tumor progression was associated with reduced endoscopic inflammation, increased apoptosis of lamina propria T lymphocytes, and significantly reduced levels of the critical proin-flammatory cytokines interleukin (IL)-21 and IL-6. Administration of hyper IL-6 abrogated protection from tumor progression in NFATc2-knockout mice and restored tumor incidence to control levels. Taken together, our findings highlight a pivotal role for NFATc2 in the establishment of inflammation-associated colorectal tumors mediated by control of IL-6 expression.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
CHRONIC INTESTINAL INFLAMMATION; T-CELL-ACTIVATION; COLORECTAL-CANCER; ULCERATIVE-COLITIS; SIGNALING PATHWAY; TUMOR PROGRESSION; NUCLEAR FACTOR; BOWEL-DISEASE; IN-VIVO; EXPRESSION
ISSN (print) / ISBN
0008-5472
e-ISSN
1538-7445
Journal
Cancer Research
Quellenangaben
Volume: 72,
Issue: 17,
Pages: 4340-4350
Publisher
American Association for Cancer Research (AACR)
Publishing Place
Philadelphia, Pa.
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes Research (IDF)