title: Involvement of activation-induced cytidine deaminase in skin cancer development.
abstract: 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.
authors.forename: Taichiro
authors.initials: T
authors.lastname: Nonaka
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Toda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hiai
authors.forename: Munehiro
authors.initials: M
authors.lastname: Uemura
authors.forename: Motonobu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Ryo
authors.initials: R
authors.lastname: Asato
authors.forename: Yukari
authors.initials: Y
authors.lastname: Hattori
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Bessho
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Minato
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D009154:Mutation; D009374:Neoplasms, Experimental / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009928:Organ Specificity; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000201:enzymology* / Q000473:pathology; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D016159:Tumor Suppressor Protein p53; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase; D016283:Proto-Oncogene Proteins p21(ras)