Department of Dermatology, University Hospital Aachen, Pauwelsstr. 30, 52074 Aachen, Germany.
J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):383-6. doi: 10.1016/j.jsbmb.2010.03.003. Epub 2010 Mar 7.
Peroxisome proliferator-activated receptor (PPAR) and vitamin D receptor (VDR) signaling pathways regulate a multitude of genes that are of importance for a multitude of cellular functions including cell proliferation, cell differentiation, immune responses and apoptosis. Ligands and other agents influencing the PPAR and VDR signaling pathways have been shown to reveal chemopreventive potential by mediating tumor suppressive activities in a variety of human cancers. Use of these compounds may represent a potential novel strategy to prevent melanoma pathogenesis and to inhibit melanoma progression. We recently showed that 1,25-dihydroxyvitamin D3 and some of the investigated PPAR ligands inhibited proliferation of the human melanoma cell line MeWo. In addition to this, our results gave an indication of an interconnection of the PPAR and VDR signaling pathways at the level of cross-regulation of their respective transcription factor mRNA levels. The provided link between VDR and PPAR may play an important role in treatment and prevention of melanoma. This review summarizes the currently available data on the roles of the PPARs and the VDR in pathogenesis and progression of melanoma as well as their role as promising future therapeutic targets.
过氧化物酶体增殖物激活受体 (PPAR) 和维生素 D 受体 (VDR) 信号通路调节着大量对细胞增殖、细胞分化、免疫反应和细胞凋亡等多种细胞功能很重要的基因。已证实，影响 PPAR 和 VDR 信号通路的配体和其他药物可通过介导多种人类癌症中的肿瘤抑制活性，显示出化学预防潜力。这些化合物的使用可能代表了预防黑色素瘤发病机制和抑制黑色素瘤进展的一种潜在的新策略。我们最近表明，1,25-二羟维生素 D3 和一些研究的 PPAR 配体抑制了人黑色素瘤细胞系 MeWo 的增殖。除此之外，我们的结果还表明，在各自转录因子 mRNA 水平的交叉调控方面，PPAR 和 VDR 信号通路之间存在着相互联系。VDR 和 PPAR 之间的这种联系可能在黑色素瘤的治疗和预防中起着重要作用。这篇综述总结了目前关于 PPAR 和 VDR 在黑色素瘤发病机制和进展中的作用及其作为有前途的治疗靶点的作用的相关数据。
