The Effects of Helicobacter pylori on the
Cadherin-catenin Complex
James Rhodri Bebb 1*, Lopa Leach 2, Abed Zaitoun 3, Neil Hand 3, Darren Letley 1, Rachael Thomas 1 and John C Atherton 1
1 Wolfson Centre for Digestive Diseases and Institute of Infections, Inflammation and Immunity
2 Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences
3 Department of Histopathology
* To whom correspondence should be addressed. E-mail: jamesbebb{at}doctors.org.uk.
Accepted 5 February 2006
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Abstract |
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Aims: The cadherin-catenin complex is the key component of the adherens junction in epithelial cells, and alterations
in this complex are implicated in gastric adenocarcinoma. Germline mutations in E-cadherin have been described in diffuse-type gastric adenocarcinoma. H. pylori infection is the first stage in gastric carcinogenesis, so we aimed to show whether H. pylori was associated with changes in the complex, and whether this was affected by strain virulence.
Methods: We performed co-cultures of epithelial cell lines with H. pylori using wild-type pathogenic and non-pathogenic H. pylori strains and CagE null and VacA null isogenic mutants. We also took gastric biopsy specimens at endoscopy from H. pylori-infected (n=17) and uninfected (n=15) patients and assessed E-cadherin and 
-catenin expression by immunohistochemistry. We PCR-typed H. pylori from these patients for cagE and vacA.
Results: Our in vitro studies showed that co-culture with a pathogenic strain of H. pylori lead to disruption of epithelial junctional -catenin expression but without evidence of nuclear translocation or signalling. This effect was independent of a functional cag pathogenicity island and vacuolating activity, but dependent on live bacteria. There were no significant differences in -catenin or E-cadherin expression in H. pylori infected and uninfected gastric biopsies.
Conclusion: Acute H. pylori infection disrupts junctional -catenin in vitro but chronic infection by H. pylori has no effect on E-cadherin and -catenin in gastric biopsies at the initial gastritis stage of the proposed Correa pathway of gastric carcinogenesis. We cannot rule out a later effect at the stages of atrophy or intestinal metaplasia.
Key Words:
Helicobacter pylori, cancer, gastritis, inflammation, stomach
