Kamradt Jörn, Rafi Leyla, Mitschele Tanja, Meineke Viktor, Gärtner Barbara C, Wolfgang Tilgen, Holick Michael F, Reichrath Jörg
Department of Dermatology, University of Saarland, Kirrberger Str., 66421 Homburg/Saar, Germany.
Recent Results Cancer Res. 2003;164:259-69. doi: 10.1007/978-3-642-55580-0_19.
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.
1,25 - 二羟基维生素D3是维生素D的生物活性代谢产物,对角质形成细胞的生长和分化有重大影响,因此已成功用于治疗增殖性皮肤病。我们现在使用免疫组织化学和定量实时PCR技术,对皮肤基底细胞癌(BCC)和鳞状细胞癌(SCC)中的维生素D系统关键成分(维生素D受体、1α - 羟化酶、24 - 羟化酶和25 - 羟化酶)进行了表征。此外,还测定了这些肿瘤的增殖活性(Ki - 67表达)、分化状态(细胞角蛋白10和转谷氨酰胺酶K表达)、凋亡率(TUNEL检测)以及维生素D受体主要异源二聚体伴侣(视黄酸X受体)的丰度,并将其与维生素D系统的成分相关联。我们的研究结果表明,维生素D系统可能对基底细胞癌和鳞状细胞癌的生长行为非常重要,并且具有较少高钙血症副作用的新型维生素D类似物可能对预防或治疗这些肿瘤有效。