title: Expression of activation-induced cytidine deaminase in oral epithelial dysplasia and oral squamous cell carcinoma.
abstract: Oral epithelial dysplasia is thought to be a precursor state of carcinogenesis and may harbor gene alterations. Recently, it was reported that gene editing enzyme, activation-induced cytidine deaminase (AID), is expressed in precursor and cancer epithelial cells during carcinogenesis associated with chronic inflammation/infection and that this enzyme induces mutation of tumor-suppressor genes. Thus, AID may have a role in carcinogenesis via oral epithelial dysplasia. In this study, we classified oral mucosal epithelium exhibiting epithelial dysplasia as squamous intraepithelial neoplasia (SIN) grades 1-3, according to the 2005 World Health Organization classification, and used immunohistochemical techniques to examine AID expression in oral mucosal epithelium exhibiting SIN and oral cancer tissues. AID was observed in prickle cells in oral mucosal epithelium with epithelial dysplasia and in oral cancer cells. Additionally, to investigate the mechanism of AID expression and its role in cancer progression, we incubated the oral cancer cell line HSC-2 with inflammatory cytokines. In the HSC-2 cell line, AID expression was enhanced by TNF-α via NF-κB activation and promoted expression of N-cadherin by regulating Snail expression. These findings suggest that AID has a role in the development of oral epithelial dysplasia and promotes progression of oral cancer.
authors.affiliation: Division of Pathology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujinami
authors.forename: Harumi
authors.initials: H
authors.lastname: Inoue
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Fumio
authors.initials: F
authors.lastname: Ide
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kusama
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D003564:Cytidine Deaminase / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000201:enzymology / Q000473:pathology*; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000473:pathology; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase