Date of Award

Spring 2011

Author's School

College of Arts & Sciences

Author's Department/Program



Background: p38α MAPK (p38) is a tumor suppressor known to be mutated in human cancers. Our lab has recently developed a mouse model for testing p38 function, specifically in the intestine in vivo. We therefore, sought to determine the effect of intestine-targeted p38 deletion on tumorigenesis in the colon. Methods: p38 was deleted in mice, specifically in the intestinal mucosa and an azoxymethane (AOM) and dextran sodium sulfate (DSS) protocol was used to drive tumor development. Four groups of mice were studied: wild type (WT) mice given water (WT H2O), WT mice given DSS (WT DSS), p38-null mice given water (KO H2O), and p38-null mice administered DSS (KO DSS). Results: We found both WT and p38-null mice developed tumors after treatment with AOM and DSS. While WT DSS (5 of 8) were just as likely as the KO DSS mice (9 of 11) to develop colonic tumors, the KO DSS group had significantly more tumors (1.00 +/- 0.38 vs 4.09 +/-1.23, p<.05). KO DSS mice also tended to have a greater tumor burden, although these differences were not statistically significant (5.45 +/- 2.20 vs 20.80 +/- 7.65 mm2, p=0.18). WT DSS and KO DSS groups had similar areas of inflamed colon (2.41 +/- 0.61% vs 3.17 +/- 0.68%, p=.51). Discussion: p38α MAPK deletion augments tumorigenesis in the colon. Overall, these results support our hypothesis that enterocyte specific p38α MAPK deletion promotes colonic tumorigenesis. This study lends support for the treatment of colorectal cancers with inducers of p38α MAPK activity, particularly if they could be targeted specifically to the colonic epithelium.


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