Functional genomics of calcium channels in human melanoma cells
Functional genomics of calcium channels in human melanoma cells
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DOI：
10.1002/ijc.22621
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发表时间：
2007-07-01
影响因子：
6.4
通讯作者：
Timar, Jozsef
中科院分区：
文献类型：
--
作者：
Deli, Tamas;Varga, Norbert;Timar, Jozsef
自从发现WNT信号在黑色素瘤发生中的作用以来，人黑色素瘤中的Ca 2+信号是深入研究的焦点。基因组和功能研究指出了各种钙离子通道在黑色素瘤中的重要作用，但这些数据是相互矛盾的。在本研究中，我们清楚地表明，在许多不同的方式，包括微阵列分析，DNA测序和免疫细胞化学，各种人类黑色素瘤细胞系和黑色素瘤组织过表达兰尼碱受体2型（RyR 2）和表达P2 X（7）通道蛋白相比，黑色素细胞。这些通道，虽然保留了它们的一些通常的特征和药理学性质，但在黑色素瘤细胞中显示出独特的功能，包括两种分子之间的功能性相互作用。与P2 X7不同，RyR 2不作为钙通道发挥作用。另一方面，P2 X7受体在黑色素瘤细胞中具有抗凋亡功能，因为ATP激活抑制诱导的凋亡，而基因表达的敲低显著增强了这一功能。(C)2007 Wiley-Liss，Inc.
Ca2+ -signaling of human melanoma is in the focus of intensive research since the identification of the role of WNT-signaling in melanomagenesis. Genomic and functional studies pointed to the important role of various Ca2+ channels in melanoma, but these data were contradictory. In the present study we clearly demonstrate, in a number of different ways including microarray analysis, DNA sequencing and immunocytochemistry, that various human melanoma cell lines and melanoma tissues overexpress ryanodine receptor type 2 (RyR2) and express P2X(7) channel proteins as compared to melanocytes. These channels, although retain some of their usual characteristics and pharmacological properties, display unique features in melanoma cells, including a functional interaction between the two molecules. Unlike P2X7, RyR2 does not function as a calcium channel. On the other hand, the P2X7 receptor has an antiapoptotic function in melanoma cells, since ATP-activation suppresses induced apoptosis, while knock down of the gene expression significantly enhances that. (C) 2007 Wiley-Liss, Inc.