Vitamin D receptor mediates DNA repair and is UV-inducible in intact epidermis but not cultured keratinocytes

While providing a powerful approach for studying epidermal biology, cultured keratinocytes may imperfectly model a three-dimensional epidermis in which cells are architecturally ordered. We report two important examples of the limitations of cultured keratinocytes in understanding vitamin D receptor (VDR) photobiology in murine skin. Recently, the vitamin D signaling pathway has been implicated in skin cancer prevention through its role in cellular responses to ultraviolet B radiation (UVB)-induced DNA damage, and demonstrations that VDR−/− mice are susceptible to UVB-induced epidermal tumors (Ellison et al., 2008; Mason et al., 2010; Quigley et al., 2009; Teichert et al., 2011). VDR's transactivation of certain genes is also mediated by a subunit of the nucleotide excision repair (NER)/transcription factor, TFIIH (Drané et al., 2004), further suggesting a potential interaction between VDR and DNA repair.