Transcription Factor NFATc2 Controls the Emergence of Colon Cancer Associated with IL-6–Dependent Colitis
2012; American Association for Cancer Research; Volume: 72; Issue: 17 Linguagem: Inglês
10.1158/0008-5472.can-11-4155
ISSN1538-7445
AutoresKatharina Gerlach, Carolin Daniel, Hans A. Lehr, Alexei Nikolaev, Thomas Gerlach, Raja Atreya, Stefan Rose‐John, Markus F. Neurath, Benno Weigmann,
Tópico(s)NF-κB Signaling Pathways
ResumoAbstract 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.
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