Helicobacter pylori-mediated dysregulation of p120-catenin and matrix metalloproteinase-7
Ogden, Seth Rayborn
Gastric adenocarcinoma is strongly associated with the presence of H. pylori, and both microbial and host factors influence the risk for carcinogenesis. A novel role for H. pylori in the stimulation of the p120ctn/Kaiso signaling axis leading to relief of Kaiso-mediated repression of mmp-7 transcription in vitro was identified. Increased expression of MMP-7 in response to H. pylori infection may alter a number of processes involved in carcinogenesis, including the inflammatory response, proliferation, and apoptosis. Bacterial challenge of mice deficient in MMP-7 resulted in enhanced inflammation and cellular turnover when compared to wild type mice, suggesting that MMP-7 may serve a protective role within H. pylori-infected gastric mucosa. Taken together, these data indicate that H. pylori stimulates increased gene transcription through dysregulation of a number of signaling pathways and that upregulation of these host effectors mediates the development of malignant lesions.