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.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03032009-131726 |
| Date | 03 March 2009 |
| Creators | Ogden, Seth Rayborn |
| Contributors | Timothy L. Cover, Barbara Fingleton, Albert B. Reynolds, Richard M. Peek, Jr. |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-03032009-131726/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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