p120 and Kaiso regulate Helicobacter pylori-induced expression of matrix metalloproteinase-7.

Ogden SR, Wroblewski LE, Weydig C, Romero-Gallo J, O'Brien DP, Israel DA, Krishna US, Fingleton B, Reynolds AB, Wessler S, Peek RM
Mol Biol Cell. 2008 19 (10): 4110-21

PMID: 18653469 · PMCID: PMC2555941 · DOI:10.1091/mbc.e08-03-0283

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 cag- and 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.

MeSH Terms (18)

Active Transport, Cell Nucleus Antigens, Bacterial Bacterial Proteins Catenins Cell Adhesion Molecules Gene Expression Regulation, Bacterial Gene Expression Regulation, Neoplastic Helicobacter Infections Helicobacter pylori Humans Matrix Metalloproteinase 7 Phosphoproteins RNA, Messenger RNA, Small Interfering Stomach Neoplasms Subcellular Fractions Transcription, Genetic Transcription Factors

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