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Gerlach, K.* ; Daniel, C. ; Lehr, H.A.* ; Nikolaev, A.* ; Gerlach, T.* ; Atreya, R.* ; Rose-John, S.* ; Neurath, M.F.* ; Weigmann, B.*

Transcription factor NFATc2 controls the emergence of colon cancer associated with IL-6-dependent colitis.

Cancer Res. 72, 4340-4350 (2012)
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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
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