Vitamin D and skin cancer
2004
Bikle, D.D.
Skin cancer is the most common cancer afflicting humans. These cancers include melanomas and 2 types of malignant keratinocytes: basal-cell carcinomas (BCC) and squamous-cell carcinomas (SCC). UV light exposure is linked to the incidence of these cancers. On the other hand, the skin is the major source of vitamin D-3 (cholecalciferol) and UV light is critical for its formation. Keratinocytes can convert vitamin D-3 to its hormonal form, 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] (calcitriol). 1,25(OH)2D3 in turn stimulates the differentiation of keratinocytes, raising the hope that 1,25(OH)2D3 may prevent the development of malignancies in these cells. We identified a number of mechanisms by which 1,25(OH)2D3 regulates the differentiation of keratinocytes and explored where this regulation breaks down in SCCs. 1,25(OH)2D3 regulates gene expression by activating the vitamin D receptor (VDR). When activated, the VDR binds to one of two coactivator complexes: DRIP or p160/SRC. Binding to DRIP occurs in the undifferentiated keratinocyte, but, as the cell differentiates, DRIP205 levels fall and p160/SRC binding takes over as SRC3 expression increases. SCCs fail to respond to the prodifferentiating actions of 1,25(OH)2D3. These cells have normal levels of VDR and normal binding of VDR to vitamin D response elements. However, they overexpress DRIP205 such that the p160/SRC complex is blocked from binding to VDR. We hypothesize that failure of 1,25(OH)2D3 to induce differentiation in SCCs lies at least in part with its failure to induce the replacement of the DRIP complex with the SRC complex in the promoters of genes required for differentiation.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
المعلومات البيبليوغرافية
تم تزويد هذا السجل من قبل National Agricultural Library
