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Stomach Bug’s Cancer-Causing Ways

Disruption of tumor suppressor may explain increased gastric cancer risk

November 12, 2010 | LEIGH MACMILLAN

Helicobacter pylori – a bacterial species found in the stomachs of more than half of all humans – is the strongest known risk factor for gastric adenocarcinoma, but only a fraction of infected persons will develop cancer.

Alexander Zaika, Ph.D., and colleagues investigated the regulation of p53, a tumor suppressor that might counteract oncogenic signaling pathways, in H. pylori-infected Mongolian gerbils and gastric epithelial cells co-cultured with the bacterium. They found that H. pylori decreases p53 levels by increasing ubiquitination (a modification that targets p53 for destruction) and proteasomal degradation in a pathway involving the proteins AKT1 and HDM2. The H. pylori virulence factor CagA mediated these effects, and the reduced levels of p53 increased the survival of cells with DNA damage.

The findings, reported in the October issue of Gastroenterology, suggest that H. pylori-induced dysregulation of p53 may be a mechanism by which the bug increases the risk of gastric cancer in infected individuals.

For other research highlights from Vanderbilt University Medical Center laboratories, see ‘Aliquots‘ in the VUMC Reporter.