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PDF file - 112K, expression of cox-2 and VEGF

PDF file - 547K, DSS Colitis

PDF file - 419K, table of patient data for supplementary figures

PDF file - 106K

PDF file - 559K, expression of IL-11 and IL-22

PDF file - 330K, proliferation staining KI-67 in cryosection

PDF file - 547K, cytokineproduction of spleen cells and LPMC

PDF file - 589K, expresion of IL-1b and IFN-g

PDF file - 660K, staining of EpCAM and IL-6 in cytospin preparation

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 proinflammatory 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. Cancer Res; 72(17); 4340–50. ©2012 AACR.