Titre
Inverse relationship between increased apoptosis and decreased skin cancer in UV-irradiated CD1d-/- mice
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Matsumura, Y.
Auteure/Auteur
Moodycliffe, A. M.
Auteure/Auteur
Nghiem, D. X.
Auteure/Auteur
Ullrich, S. E.
Auteure/Auteur
Ananthaswamy, H. N.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0031-8655
Statut éditorial
Publié
Date de publication
2005-02
Volume
81
Numéro
1
Première page
46
Dernière page/numéro d’article
51
Notes
Journal Article --- Old month value: Jan-Feb
Résumé
We previously demonstrated that CD1d knockout mice were resistant to ultraviolet (UV)-induced immunosuppression. Because immune suppression is a critical factor in the development of UV-induced skin cancers, we 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. To investigate the mechanisms involved in the resistance of CD1d-/- mice to UV-induced carcinogenesis, we determined the time course and kinetics of keratinocyte cell death after UV irradiation. After acute UV exposure, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL)-positive keratinocytes were eliminated from the skin of WT mice by 72 h post-UV, but they still persisted until 96 h in CD1d-/- mice. The kinetics of p53 protein expression closely followed the kinetics of apoptotic cell death. Chronic UV irradiation resulted in induction of a significantly higher number of apoptotic keratinocytes in CD1d-/- than WT mice. In addition, epidermis and dermis from chronically UV-irradiated CD1d-/- mice harbored significantly fewer p53 mutations than WT mice. These results indicate that the resistance of CD1d-/- mice to UV carcinogenesis may be due to increased cell death and elimination of keratinocytes and fibroblasts containing DNA damage and p53 mutations.
Sujets
PID Serval
serval:BIB_61510E62BE1F
PMID
Date de création
2008-01-25T15:50:37.342Z
Date de création dans IRIS
2025-05-20T20:59:06Z