Resistance of CD1d-/- mice to ultraviolet-induced skin cancer is associated with increased apoptosis

Détails

ID Serval
serval:BIB_C8A55CAE84C9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Resistance of CD1d-/- mice to ultraviolet-induced skin cancer is associated with increased apoptosis
Périodique
American Journal of Pathology
Auteur(s)
Matsumura  Y., Moodycliffe  A. M., Nghiem  D. X., Ullrich  S. E., Ananthaswamy  H. N.
ISSN
0002-9440 (Print)
Statut éditorial
Publié
Date de publication
09/2004
Volume
165
Numéro
3
Pages
879-887
Notes
Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. --- Old month value: Sep
Résumé
Inhibition of p53-induced epidermal apoptosis, generation of p53 mutations, and suppressor T cells are the critical events responsible for the induction and development of UV-induced skin cancers. Recently, we demonstrated that CD1d knockout mice were resistant to UV-induced immunosuppression, prompting us to further address the role of CD1d in regulating UV carcinogenesis. We, therefore, investigated the response of wild-type (WT) and CD1d-/- mice to UV carcinogenesis. We found that although 100% of WT mice developed skin tumors after 45 weeks of UV irradiation, only 60% of CD1d-/- mice developed skin tumors. Surprisingly, keratinocytes and fibroblasts from CD1d-/- mice were more sensitive to UV-induced apoptosis and persisted longer than cells derived from WT mice. In addition, epidermis and dermis taken from chronically UV-irradiated CD1d-/- mice harbored significantly fewer p53 mutations than WT mice. Our findings identify an unexpected and novel function for CD1d as a critical molecule regulating UV carcinogenesis, by inhibiting apoptosis to prevent elimination of potentially malignant keratinocytes and fibroblasts.
Mots-clé
Animals Antigens, CD1/genetics/*physiology *Apoptosis/genetics/radiation effects Female Fibroblasts/radiation effects *Genetic Predisposition to Disease Homozygote In Situ Nick-End Labeling Keratinocytes/radiation effects Male Mice Mice, Knockout Mutation/genetics Neoplasms, Radiation-Induced/genetics/*pathology/prevention & control *Radiation Tolerance Skin/radiation effects *Skin Neoplasms/genetics/*pathology/prevention & control Tumor Suppressor Protein p53/genetics/metabolism Ultraviolet Rays
Pubmed
Web of science
Création de la notice
25/01/2008 17:50
Dernière modification de la notice
03/03/2018 21:21
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