title: Role of activation-induced cytidine deaminase in inflammation-associated cancer development.
abstract: Human cancer is a genetic disease resulting from the stepwise accumulation of genetic alterations in various tumor-related genes. Normal mutation rates, however, cannot account for the abundant genetic changes accumulated in tumor cells, suggesting that certain molecular mechanisms underlie such a large number of genetic alterations. Activation-induced cytidine deaminase (AID), a nucleotide-editing enzyme that triggers DNA alterations and double-strand DNA breaks in the immunoglobulin gene, has been identified in activated B lymphocytes. Recent studies revealed that AID-mediated genotoxic effects target not only immunoglobulin genes but also a variety of other genes in both B lymphocytes and non-lymphoid cells. Consistent with the finding that several transcription factors including nuclear factor-κB (NF-κB) mediate AID expression in B cells, proinflammatory cytokine stimulation of several types of gastrointestinal epithelial cells, such as gastric, colonic, hepatic, and biliary epithelium, induces aberrant AID expression through the NF-κB signaling pathway. In vivo studies revealed that constitutive AID expression promotes the tumorigenic pathway by enhancing the susceptibility to mutagenesis in a variety of epithelial organs. The activity of AID as a genome mutator provides a new avenue for studies aimed at understanding mutagenesis mechanisms during carcinogenesis.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Marusawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takai
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004847:Epithelial Cells / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D017578:Immunoglobulin Class Switching; D007249:Inflammation; D016296:Mutagenesis; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D016328:NF-kappa B; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase