| First Author | Matsumura Y | Year | 2004 |
| Journal | Am J Pathol | Volume | 165 |
| Issue | 3 | Pages | 879-87 |
| PubMed ID | 15331412 | Mgi Jnum | J:92422 |
| Mgi Id | MGI:3052603 | Doi | 10.1016/S0002-9440(10)63350-0 |
| Citation | Matsumura Y, et al. (2004) Resistance of CD1d-/- mice to ultraviolet-induced skin cancer is associated with increased apoptosis. Am J Pathol 165(3):879-87 |
| abstractText | 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. |
