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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
Keywords
  • 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
Abstract
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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