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• W2470895903 abstract "1,25 dihydroxyvitamin D (1,25(OH)2D), the active metabolite of vitamin D, and calcium regulate epidermal differentiation. 1,25(OH)2D exerts its effects through the vitamin D receptor (VDR), a transcription factor in the nuclear hormone receptor family, whereas calcium acts through the calcium sensing receptor (Casr), a membrane bound member of the G protein coupled receptor family. We have developed mouse models in which the Vdr and Casr have been deleted in the epidermis ((epid) Vdr (-∕-) and (epid) Casr (-∕-)). Both genotypes show abnormalities in calcium induced epidermal differentiation in vivo and in vitro, associated with altered hedgehog (HH) and β-catenin signaling that when abnormally expressed lead to basal cell carcinomas (BCC) and trichofolliculomas, respectively. The Vdr (-∕-) mice are susceptible to tumor formation following UVB or chemical carcinogen exposure. More recently we found that the keratinocytes from these mice over express long non-coding RNA (lncRNA) oncogenes such as H19 and under express lncRNA tumor suppressors such as lincRNA-21. Spontaneous tumors have not been observed in either the (epid) Vdr (-∕-) or (epid) Casr (-∕-). But in mice with epidermal specific deletion of both Vdr and Casr ((epid) Vdr (-∕-)/(epid) Casr (-∕-) [DKO]) tumor formation occurs spontaneously when the DKO mice are placed on a low calcium diet. These results demonstrate important interactions between vitamin D and calcium signaling through their respective receptors that lead to cancer when these signals are disrupted. The roles of the β-catenin, hedgehog, and lncRNA pathways in predisposing the epidermis to tumor formation when vitamin D and calcium signaling are disrupted will be discussed." @default.
• W2470895903 created "2016-07-22" @default.
• W2470895903 creator A5031553352 @default.
• W2470895903 creator A5031984792 @default.
• W2470895903 creator A5032781101 @default.
• W2470895903 creator A5043516928 @default.
• W2470895903 creator A5066658087 @default.
• W2470895903 date "2016-07-12" @default.
• W2470895903 modified "2023-10-14" @default.
• W2470895903 title "Disruption of Vitamin D and Calcium Signaling in Keratinocytes Predisposes to Skin Cancer" @default.
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