期刊
MOLECULAR BIOLOGY OF THE CELL
卷 19, 期 10, 页码 4110-4121出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E08-03-0283
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- NCI NIH HHS [T32 CA009592] Funding Source: Medline
- NIDDK NIH HHS [P30 DK058404, DK-058404, DK-73902, R01 DK073902, R01 DK058587, DK-77955, K01 DK077955, DK-58587] Funding Source: Medline
Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, yet only a fraction of infected persons develop cancer. One H. pylori constituent that augments disease risk is the cytotoxin-associated gene (cag) pathogenicity island, which encodes a secretion system that translocates bacterial effector molecules into host cells. Matrix metalloproteinase (MMP)-7, a member of a family of enzymes with tumor-initiating properties, is overexpressed in premalignant and malignant gastric lesions, and H. pylori cag(+) strains selectively increase MMP-7 protein levels in gastric epithelial cells in vitro and in vivo. We now report that H. pylori-mediated mmp-7 induction is transcriptionally regulated via aberrant activation of p120-catenin (p120), a component of adherens junctions. H. pylori increases mmp-7 mRNA levels in a cagand p120-dependent manner and induces translocation of p120 to the nucleus in vitro and in a novel ex vivo gastric gland culture system. Nuclear translocation of p120 in response to H. pylori relieves Kaiso-mediated transcriptional repression of mmp-7, which is implicated in tumorigenesis. These results indicate that selective and coordinated induction of mmp-7 expression by H. pylori cag(+) isolates may explain in part the augmentation in gastric cancer risk associated with these strains.
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