| セッション情報 |
Helicobacter Pylori Infection:Basic and Clinical Topics
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| タイトル |
IF2-3 Helicobacter pylori CagA Protein Variation Associated with Gastric Cancer
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| 演者 |
Takeshi Azuma（Department of GastroenterologyKobe University School of MedicineJapan） |
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| 抄録 |
CagA is directly inj・ected from the H． pyiori into thecells via the bacterial type IV secretion system andundergoes tyrosine phosphorylation in the host cells． We recently discovered that translocated CagAforms a physical complex with SHP－2and stimulates phosphatase activity． SHP－2 is known to play an im－portant positive role in mitogenic signal transduction． Deregulation of SHP－2 by CagA may induce abnor－mal proliferation and movement of gastric epithelial cellsln． additionthe CagA protein is polymorphic．We discovered that predominant CagA proteins isolated in East Asiawhere gastric cancer is prevalenthave a distinct sequence at the phosphorylation site of CagA． East Asian－specific sequence confersstronger SHP－2 binding and transforming activities to Western CagA． The potential of CagA to disturbhost cell functions as a virulence factor could be determined by the degree of SHP－2 binding activity． Thediversity of the CagA phosphorylation site which collectively determines binding affinity of CagA to SHP－2may be an important variable in determining the clinieal outcome of infection by difiierent H． pyloristrains． We examined the CagA diversity of H． pylori i solated from chronic gastritis and gastric cancer pa一・tients in Asian countries． We also ’imvestigated the distribution of CagA protein diversity in the world us－ing data deposited in the GenBank． The prevalence of East Asian CagA was significantly higher in pa－tients with gastric cancer than in patients with chronic gastritis． The much greater magnitude of risk ob－served with East Asian CagApositive Hpylori infection． The prevalence of East Asian CagA－positivestrains appeared to be asso￠iated with the rate of’ gastric cancer mortality． Thereforepatients harboringEast Asian CagA。positive且pylori’are at a higher risk for developing gastric cancer thall those ir［fectedwith Western CagA－positive strains． |
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