The stomach-dwelling bacterium Helicobacter pylori infects about half of the world’s population and is a strong risk factor for gastric cancer. Emerging evidence suggests that during precancerous stages, H. pylori compromises the function of p53 – a tumor suppressor protein that responds to cellular stress and DNA damage.
Although p53 is well characterized as a tumor suppressor, recently discovered p53 isoforms (different versions of the protein) may actually promote tumorigenesis. Alexander Zaika, Ph.D., associate professor of Surgery, and colleagues now demonstrate that the interaction of H. pylori with gastric epithelial cells increases the production of a set of p53 isoforms that inhibit p53 and p73 (another tumor suppressor) and increase survival of infected cells.
The results, reported in the Sept. 18 Proceedings of the National Academy of Sciences, provide insights into the regulation of the p53 protein and suggest that a link between p53 isoforms and H. pylori may be an important contributor to the increased risk for gastric cancer associated with the bug.
This research was supported by grants from the National Cancer Institute (CA138833, CA068485) and the National Institute of Diabetes and Digestive and Kidney Diseases (DK058404) of the National Institutes of Health.
