Helicobacter Pylori CagA and Gastric Carcinogenesis

Ri-Nan Zheng,Shu-Rong Li,Asaka Masahiro

doi:10.7314/apjcp.2012.13.12.6305

Ri-Nan Zheng, Shu-Rong Li + Show 1 more

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https://doi.org/10.7314/apjcp.2012.13.12.6305

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Abstract

This study aimed to demonstrate the tyrosine phosphorylation motif (TPM) and 3' region structure of the Helicobacter pylori CagA gene as well as its SHP-2 binding activity in AGS cells and relation to gastric carcinogenesis. Sixteen clinical isolate H. pylori strains from eight duodenal ulcer and eight gastric adenocarcinoma patients were studied for CagA repeat sequence EPIYA motifs, C-terminal structure, and western blot analysis of CagA protein expression, translocation, and SHP-2 binding in AGS cells. Except for strain 547, all strains from the gastric adenocarcinoma patients were positive for CagA by PCR and had three EPIYA copy motifs. Western blotting showed that all strains were positive for CagA protein expression (100%), CagA protein translocation (100%), and SHP-2 binding (100%). CagA protein expression was significantly higher in the gastric adenocarcinoma patients than in the duodenal ulcer patients (P=0.0023). CagA protein translocation and SHP-2 binding in the gastric adenocarcinoma patients were higher than those in the duodenal ulcer patients, but no significant differences were found between the two groups (P=0.59, P=0.21, respectively). The TPMs and 3' region structures of the H. pylori CagA gene in the duodenal ulcer and gastric adenocarcinoma patients have no significant differences.

Highlights

Helicobacter pylori colonises the stomachs of 50% of the world’s population and is associated with the development of gastroduodenal diseases, such as peptic ulcer disease, atrophic gastritis, and distal gastric adenocarcinoma and lymphoma
Sixteen clinical isolate H. pylori strains from eight duodenal ulcer and eight gastric adenocarcinoma patients were studied for CagA repeat sequence EPIYA motifs, C-terminal structure, and western blot analysis of CagA protein expression, translocation, and SHP-2 binding in AGS cells
Murakita et al reported that tox+ H. pylori isolates are more prevalent in patients with severe atrophic gastritis and that the cytotoxic activities in H. pylori isolates from patients with severe atrophic gastritis are much higher than those from patients with mild atrophic gastritis in Japan (Murakita et al, 1996)

Summary

Introduction

Helicobacter pylori colonises the stomachs of 50% of the world’s population and is associated with the development of gastroduodenal diseases, such as peptic ulcer disease, atrophic gastritis, and distal gastric adenocarcinoma and lymphoma. Most Japanese H. pylori strains are positive for CagA. The prevalence of both gastric cancer and atrophic gastritis is extremely high in Japan (Graham and Asaka, 2010). The lineage of H. pylori isolates infecting Japanese subjects may be different from that of isolates in other parts of the world, and a specific strain may have accumulated in the Japanese population. H. pylori strains possessing the CagA gene were linked with an increased risk of developing gastric cancer and peptic ulcer (Cavalcante et al, 2012; Epplein et al, 2012).

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