Helicobacter pylori induces somatic mutations in TP53 via overexpression of CHAC1 in infected gastric epithelial cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19077
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: ITO Takashi 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (20516314)
• Research Collaborator: WADA Yuriko ; KAKEGAWA Tomoya
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: cagA / CHAC1 / グルタチオン / H. pylori / p53 / ROS

Outline of Final Research Achievements

Cation transport regulator 1 (CHAC1) has γ-glutamylcyclotransferase activity that degrades glutathione. We found that cagA-positive Helicobacter pylori (H. pylori) infection triggered CHAC1 overexpression in human gastric epithelial (AGS) cells leading to glutathione degradation and the accumulation of reactive oxygen species (ROS). Nucleotide alterations in the TP53 tumour suppressor gene were induced in AGS cells overexpressing CHAC1, whereas no mutations were detected in cells overexpressing a catalytically inactive mutant of CHAC1. A high frequency of TP53 mutations occurred in H. pylori-infected AGS cells but this was prevented in cells transfected with CHAC1 siRNA. These findings indicate that H. pylori-mediated CHAC1 overexpression degrades intracellular glutathione, allowing the accumulation of ROS which subsequently causes mutations that could contribute to the development of gastric cancer.

Free Research Field

病理学