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

The American Journal of Pathology
Yasuhiro MatsumuraH N Ananthaswamy

Abstract

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.

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Citations

Feb 9, 2013·Photomedicine and Laser Surgery·Timon Cheng-Yi LiuXing-Er Li
Nov 29, 2005·Journal of Clinical Pathology·M A AdlyM Hussein
Jul 23, 2013·The Journal of Investigative Dermatology·Stephan RyserAngus M Moodycliffe
Mar 21, 2008·Photochemistry and Photobiology·Gary M Halliday, J Guy Lyons
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica L PalmerDouglas E Faunce
Apr 27, 2019·International Journal of Molecular Sciences·Matthew J BottomleyIrene Leigh
Sep 17, 2009·Molecular Biology Reports·Shi-Guang ZhangZhi Du
May 7, 2014·Journal of Leukocyte Biology·Sara J McKeeGraham R Leggatt

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