| First Author | Karasawa F | Year | 2012 |
| Journal | J Clin Invest | Volume | 122 |
| Issue | 3 | Pages | 923-34 |
| PubMed ID | 22307328 | Mgi Jnum | J:184485 |
| Mgi Id | MGI:5424091 | Doi | 10.1172/JCI59087 |
| Citation | Karasawa F, et al. (2012) Essential role of gastric gland mucin in preventing gastric cancer in mice. J Clin Invest 122(3):923-34 |
| abstractText | Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides (O-glycans) having terminal alpha1,4-linked N-acetylglucosamine residues (alphaGlcNAc). Previously, we identified human alpha1,4-N-acetylglucosaminyltransferase (alpha4GnT), which is responsible for the O-glycan biosynthesis and characterized alphaGlcNAc function in suppressing Helicobacter pylori in vitro. In the present study, we engineered A4gnt(-/-) mice to better understand its role in vivo. A4gnt(-/-) mice showed complete lack of alphaGlcNAc expression in gastric gland mucin. Surprisingly, all the mutant mice developed gastric adenocarcinoma through a hyperplasia-dysplasia-carcinoma sequence in the absence of H. pylori infection. Microarray and quantitative RT-PCR analysis revealed upregulation of genes encoding inflammatory chemokine ligands, proinflammatory cytokines, and growth factors, such as Ccl2, Il-11, and Hgf in the gastric mucosa of A4gnt(-/-) mice. Further supporting an important role for this O-glycan in cancer progression, we also observed significantly reduced alphaGlcNAc in human gastric adenocarcinoma and adenoma. Our results demonstrate that the absence of alphaGlcNAc triggers gastric tumorigenesis through inflammation-associated pathways in vivo. Thus, alphaGlcNAc-terminated gastric mucin plays dual roles in preventing gastric cancer by inhibiting H. pylori infection and also suppressing tumor-promoting inflammation. |
