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Involvement of activation-induced cytidine deaminase in skin cancer development
- Source :
- Journal of Clinical Investigation. 126:1367-1382
- Publication Year :
- 2016
- Publisher :
- American Society for Clinical Investigation, 2016.
-
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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15588238 and 00219738
- Volume :
- 126
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Investigation
- Accession number :
- edsair.doi.dedup.....89f45cdafadca9161a4444eafd3182ac