| 共同演者 |
Kawamura Yuki I（Department of Gastroenterology, Research Institute, National Center for Global Health and Medicine, Japan）, Hagiwara Teruki（Department of Gastroenterology, Research Institute, National Center for Global Health and Medicine, Japan）, Otsubo Takeshi（Department of Gastroenterology, Research Institute, National Center for Global Health and Medicine, Japan）, Hashimoto Shin-ichi（Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Japan）, Oshima Kenshiro（Graduate School of Frontier Sciences, The University of Tokyo, Japan）, Hattori Masahira（Graduate School of Frontier Sciences, The University of Tokyo, Japan）, Endo Takaho A（RIKEN Genomic Sciences Center, Japan）, Toyoda Tetsuro（RIKEN Genomic Sciences Center, Japan）, Kawamura Yutaka J（Department of Surgery, Jichi Medical University Saitama Medical Center, Japan）, Konishi Fumio（Department of Surgery, Jichi Medical University Saitama Medical Center, Japan）, Yano Hideaki（Department of Surgery, National Center for Global Health and Medicine, Japan）, Saito Yukio（Department of Surgery, National Center for Global Health and Medicine, Japan）, Matsumoto Takayuki（Department of Internal Medicine, Hyogo College of Medicine, Japan）, Suzuki Hiromu（Department of Biochemistry, Sapporo Medical University, JapanDELIMITERFirst Department of Internal Medicine, Sapporo Medical University, Japan）, Toyoda Minoru（Department of Biochemistry, Sapporo Medical University, Japan） |
| 抄録 |
Some types of malignant neoplasm are characterized by epigenetic changes including DNA hypermethylation. In inflammation-related cancer, we hypothesized that DNA methylation is induced to facilitate emergent tissue regeneration in a response to inflammation. In this study, we attempted to examine this hypothesis in cancer associated with ulcerative colitis（UC）. We previously found that DNA hypermethylation and silencing of a set of glycosyltransferases was the leading cause of malignant glycosylation in gastric cancer. The Sda carbohydrate is expressed on mucin produced by goblet cells, but its loss by gene silencing causes de novo expression of sLex, which mediates cancer metastasis. In this study, we found that loss of Sda in the majority of UC cases and in UC-associated neoplasia. The methylation frequency of the Sda synthase B4GALNT2 gene was higher in the UC mucosa and UC-associated cancers than in sporadic cancer, and it reflected disease severity. Relation of cell proliferation and DNA methylation levels was also shown in vitro using colon epithelial cells. These results suggest that the loss of Sda is widely observed in UC patients but fixed by DNA methylation, which may alter cell proliferation and partially contribute to the development of precancerous mucosa in UC. |
