caa a22 4500 445888571 CHVBK 20180317145608.0 cr unu---uuuuu 170323e20110101xx s 000 0 eng 10.1007/s00535-010-0326-1 doi (NATIONALLICENCE)springer-10.1007/s00535-010-0326-1 Involvement of activation-induced cytidine deaminase in the development of colitis-associated colorectal cancers [Elektronische Daten] [Yoko Endo, Hiroyuki Marusawa, Tsutomu Chiba] Chronic inflammatory bowel disease (IBD) is an important etiologic factor in the development of colorectal cancer. However, the mechanism underlying the development of colorectal cancers through chronic inflammation is not known. Activation-induced cytidine deaminase (AID) was originally identified as an inducer of somatic hypermutation in the immunoglobulin gene. We recently found that the mutagenic activity of AID expression links inflammation to the development of cancer. Aberrant AID expression is triggered by hepatitis C virus infection in human hepatocytes or Helicobacter pylori infection in human gastric epithelial cells, and leads to the generation of somatic mutations in various tumor-related genes. Here, we review our findings relating to how AID contributes to the development of colitis-associated colorectal cancers (CACs). Immunohistochemistry revealed the enhanced expression of endogenous AID protein in not only in the inflamed colonic mucosa of ulcerative colitis patients but also CAC tumor lesions. Pro-inflammatory cytokine TNF-α induced strong aberrant expression of AID via IκB kinase-dependent NF-κB-signaling pathways in human colonic epithelial cells. Furthermore, AID expression was also elicited in response to the T helper cell-2-driven cytokines IL-4 and IL-13, which are activated in human IBD. Aberrant activation of AID in colonic cells preferentially evoked genetic mutations in the TP53 gene, whereas there were no nucleotide alterations of the APC gene. These findings suggested that pro-inflammatory cytokine-mediated aberrant expression of AID in colonic epithelial cells plays a role as a genotoxic factor that enhances genetic instability during chronic colonic inflammation, leading to CAC development. Springer, 2010 AID nationallicence Inflammatory bowel disease nationallicence Colitis-associated colorectal cancer nationallicence Cytokine nationallicence TP53 nationallicence AID : Activation-induced cytidine deaminase nationallicence TNF : Tumor necrosis factor nationallicence NF-κB : Nuclear factor κB nationallicence IKK : IκB kinase nationallicence IL : Interleukin nationallicence Endo Yoko Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, 606-8507, Kyoto, Japan aut Marusawa Hiroyuki Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, 606-8507, Kyoto, Japan aut Chiba Tsutomu Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, 606-8507, Kyoto, Japan aut Journal of Gastroenterology Springer Japan 46(2011-01-01), 6-10 0944-1174 46<6 2011 46 535 https://doi.org/10.1007/s00535-010-0326-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-010-0326-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Endo Yoko Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, 606-8507, Kyoto, Japan aut NATIONALLICENCE 700 1- Marusawa Hiroyuki Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, 606-8507, Kyoto, Japan aut NATIONALLICENCE 700 1- Chiba Tsutomu Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, 606-8507, Kyoto, Japan aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46(2011-01-01), 6-10 0944-1174 46<6 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer