Role of Helicobacter pylori CagA molecular variations in induction of host phenotypes with carcinogenic potential.
Helicobacter pylori cagA-positive strains exert population-specific risks for gastric cancer. We determined whether variations in CagA phosphorylation motifs were associated with carcinogenic or proinflammatory epithelial phenotypes induced by strains from regions with divergent cancer risks (Colombia and Nashville, TN). Motif number was significantly related to levels of CagA phosphorylation and cytoskeletal abnormalities. Precancerous isolates possessed a higher number of motifs, and precancerous strains from Nashville induced higher levels of IL-8 than Colombian strains. These results indicate that CagA variants are linked with premalignant lesions in distinct populations and that epithelial responses to these strains are selective based upon locale.
Schneider
Natasha
N
Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2279, USA.
Krishna
Uma
U
Romero-Gallo
Judith
J
Israel
Dawn A
DA
Piazuelo
M Blanca
MB
Camargo
M Constanza
MC
Sicinschi
Liviu A
LA
Schneider
Barbara G
BG
Correa
Pelayo
P
Peek
Richard M
RM
D020816:Amino Acid Motifs; D000942:Antigens, Bacterial / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000150:complications / Q000453:epidemiology / Q000382:microbiology*; D002460:Cell Line; D003105:Colombia / Q000453:epidemiology; D005260:Female; D016481:Helicobacter Infections / Q000150:complications* / Q000382:microbiology; D016480:Helicobacter pylori / Q000145:classification* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D010641:Phenotype; D010766:Phosphorylation; D020033:Protein Isoforms; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000150:complications / Q000453:epidemiology / Q000382:microbiology*; D013714:Tennessee / Q000453:epidemiology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D020033:Protein Isoforms; C080866:cagA protein, Helicobacter pylori