Analysis of the vitamin D system in cutaneous malignancies

Abstract

1,25-dihydroxyvitamin D3, the biological active metabolite of vitamin D, has great impact on keratinocyte growth and differentiation, and consequently has already been successfully used in the therapy of hyperproliferative skin disorders. We have now characterized the key components of the vitamin D system (VDR, 1alpha-OHase, 24-OHase and 25-OHase) in cutaneous basal cell carcinomas (BCC) and squamous cell carcinomas (SCC), using immunohistochemical and quantitative real-time PCR techniques. Additionally, proliferative activity (Ki-67 expression), differentiation status (cytokeratin 10 and transglutaminase K expression), rate of apoptosis (TUNEL assay) and the abundance of the main heterodimerization partners of VDR (RXRs) was determined for these tumours and correlated with the components of the Vitamin D system. Our findings indicate that the Vitamin D system may be of high importance for the growth behaviour of BCCs and SCCs and that new vitamin D analogues that exert less calcaemic side effects may be effective in the prevention or treatment of these tumours.