Ultraviolet light B (UVB) exposure induces cutaneous squamous cell carcinoma (cSCC), one of the most prevalent human cancers. Reoccurrence of cSCC in high-risk patients is prevented by oral retinoids. But oral retinoid treatment causes significant side effects; and patients develop retinoid resistance. Exactly how retinoids prevent UVB-induced cSCC is currently not well understood. Retinoid resistance blocks mechanistic studies in the leading mouse model of cSCC, the UVB exposed SKH-1 hairless mouse. To begin to understand the role of retinoids in UVB-induced cSCC we first examined the localization pattern of key retinoid metabolism proteins by immunohistochemistry 48 hours after UVB treatment of female SKH-1 mice. We next inhibited retinoic acid (RA) synthesis immediately after UVB exposure. Acute UVB increased RA synthesis, signaling, and degradation proteins in the stratum granulosum. Some of these proteins changed their localization; while other proteins just increased in intensity. In contrast, acute UVB reduced the retinoid storage protein lectin:retinol acyltransferase (LRAT) in the epidermis. Inhibiting RA synthesis disrupted the epidermis and impaired differentiation. These data suggests that repair of the epidermis after acute UVB exposure requires endogenous RA synthesis.

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Exposure to UVB light is the largest risk factor for the development of cutaneous squamous cell carcinoma, one of the most common cancers in the United States. UVB light causes changes to occur in the skin such as epidermal thickening, hyperproliferation, and alterations to epidermal differentiation. Retinoids regulate the differentiation and proliferation of the epidermis. The purpose of this study is to examine the effect of acute UVB on the expression of retinoid metabolism proteins. There is limited knowledge of how UVB may affect this pathway, and our results will allow us to gain a more complete understanding of changes in the entire retinoid metabolism pathway. We examined the expression of key retinoic acid metabolism proteins in the epidermis and hair follicle remnants 48 hours after UVB exposure in SKH‐1 mice using immunohistochemistry. UVB exposure increased the expression of retinoid synthesis, degradation, and binding proteins, and decreased the expression of the retinol storage enzyme, lectin:retinol acyltransferase (LRAT). These changes in expression suggest that acute UVB increases in the synthesis of retinoic acid in the epidermis. Many of these proteins changed their localization in the epidermis, concentrating in the more differentiated cells of the stratum granulosum and stratum corneum. This change in retinoic acid synthesis could affect the repair and normalization of UVB‐damaged epidermis. This work was supported by the Department of Human Sciences (Human Nutrition), The Molecular Carcinogenesis and Chemoprevention Program of The Ohio State University Comprehensive Cancer Center (grant P30 CA16058, National Cancer Institute) and the Center for Advanced Functional Foods Research and Entrepreneurship (CAFREE).

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