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Title page for ETD etd-03032009-131726

Type of Document Dissertation
Author Ogden, Seth Rayborn
URN etd-03032009-131726
Title Helicobacter pylori-mediated dysregulation of p120-catenin and matrix metalloproteinase-7
Degree PhD
Department Cancer Biology
Advisory Committee
Advisor Name Title
Barbara Fingleton Committee Chair
Albert B. Reynolds Committee Member
Richard M. Peek, Jr. Committee Member
Timothy L. Cover Committee Member
  • p120
  • p120-catenin
  • matrix metalloproteinase-7
  • MMP-7
  • Helicobacter pylori
  • Helicobacter pylori infections -- Pathophysiology
  • Stomach -- Cancer -- Etiology
  • Cell adhesion molecules
  • Metalloproteinases
Date of Defense 2009-02-20
Availability unrestricted
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.
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