Involvement of activation-induced cytidine deaminase in skin cancer development
| Autor: | Norio Yamamoto, Munehiro Uemura, Kazuo Kinoshita, Ryo Asato, Yukari Hattori, Yoshinobu Toda, Taichiro Nonaka, Motonobu Nakamura, Nagahiro Minato, Hiroshi Hiai, Kazuhisa Bessho |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Skin Neoplasms Ultraviolet Rays DNA damage Mice Nude Human skin medicine.disease_cause Proto-Oncogene Proteins p21(ras) Mice 03 medical and health sciences 0302 clinical medicine Cytidine Deaminase medicine Activation-induced (cytidine) deaminase Skin Squamous Cell Carcinoma Animals Humans HRAS Skin Mice Knockout Mice Inbred BALB C integumentary system biology Neoplasms Experimental General Medicine Cytidine deaminase medicine.disease 030104 developmental biology Organ Specificity 030220 oncology & carcinogenesis Mutation Immunology Carcinoma Squamous Cell biology.protein Female Tumor Suppressor Protein p53 Skin cancer Carcinogenesis Research Article |
| Zdroj: | Journal of Clinical Investigation. 126:1367-1382 |
| ISSN: | 1558-8238 0021-9738 |
| DOI: | 10.1172/jci81522 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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