@article{oai:soar-ir.repo.nii.ac.jp:00007191,
 author = {Karasawa,  Fumitoshi and Shiota,  Akira and Goso,  Yukinobu and Kobayashi,  Motohiro and Sato,  Yoshiko and Masumoto,  Junya and Fujiwara,  Maiko and Yokosawa,  Shuichi and Muraki,  Takashi and Miyagawa,  Shinichi and Ueda,  Masatsugu and Fukuda,  Michiko N. and Fukuda,  Minoru and Ishihara,  Kazuhiko and Nakayama,  Jun},
 issue = {3},
 journal = {JOURNAL OF CLINICAL INVESTIGATION},
 month = {Mar},
 note = {信州大学博士（医学）・学位論文・平成24年3月31日授与（甲第916号）・唐澤文寿, Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides (O-glycans) having terminal alpha 1,4-linked N-acetylglucosamine residues (alpha GlcNAc). Previously, we identified human alpha 1,4-N-acetylglucosaminyltransferase (alpha 4GnT), which is responsible for the O-glycan biosynthesis and characterized alpha GlcNAc 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 alpha GlcNAc 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 alpha GlcNAc in human gastric adenocarcinoma and adenoma. Our results demonstrate that the absence of alpha GlcNAc triggers gastric tumorigenesis through inflammation-associated pathways in vivo. Thus, alpha GlcNAc-terminated gastric mucin plays dual roles in preventing gastric cancer by inhibiting H. pylori infection and also suppressing tumor-promoting inflammation., Article, JOURNAL OF CLINICAL INVESTIGATION. 122(3):923-934 (2012)},
 pages = {923--934},
 title = {Essential role of gastric gland mucin in preventing gastric cancer in mice},
 volume = {122},
 year = {2012}
}