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Publication : Involvement of activation-induced cytidine deaminase in skin cancer development.

First Author  Nonaka T Year  2016
Journal  J Clin Invest Volume  126
Issue  4 Pages  1367-82
PubMed ID  26974156 Mgi Jnum  J:234660
Mgi Id  MGI:5790542 Doi  10.1172/JCI81522
Citation  Nonaka T, et al. (2016) Involvement of activation-induced cytidine deaminase in skin cancer development. J Clin Invest 126(4):1367-82
abstractText  Most skin cancers develop as the result of UV light-induced DNA damage; however, a substantial number of cases appear to occur independently of UV damage. A causal link between UV-independent skin cancers and chronic inflammation has been suspected, although the precise mechanism underlying this association is unclear. Here, we have proposed that activation-induced cytidine deaminase (AID, encoded by AICDA) links chronic inflammation and skin cancer. We demonstrated that Tg mice expressing AID in the skin spontaneously developed skin squamous cell carcinoma with Hras and Trp53 mutations. Furthermore, genetic deletion of Aicda reduced tumor incidence in a murine model of chemical-induced skin carcinogenesis. AID was expressed in human primary keratinocytes in an inflammatory stimulus-dependent manner and was detectable in human skin cancers. Together, the results of this study indicate that inflammation-induced AID expression promotes skin cancer development independently of UV damage and suggest AID as a potential target for skin cancer therapeutics.
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