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.