Laboratori d'Investigació, University of Lleida-IRBLleida, Lerida, Spain.
Pigment Cell Melanoma Res. 2012 Mar;25(2):200-12. doi: 10.1111/j.1755-148X.2012.00978.x. Epub 2012 Feb 2.
The expression of voltage-gated calcium channels (VGCCs) has not been reported previously in melanoma cells in spite of increasing evidence of a role of VGCCs in tumorigenesis and tumour progression. To address this issue we have performed an extensive RT-PCR analysis of VGCC expression in human melanocytes and a range of melanoma cell lines and biopsies. In addition, we have tested the functional expression of these channels using Ca(2+) imaging techniques and examined their relevance for the viability and proliferation of the melanoma cells. Our results show that control melanocytes and melanoma cells express channel isoforms belonging to the Ca(v) 1 and Ca(v) 2 gene families. Importantly, the expression of low voltage-activated Ca(v) 3 (T-type) channels is restricted to melanoma. We have confirmed the function of T-type channels as mediators of constitutive Ca(2+) influx in melanoma cells. Finally, pharmacological and gene silencing approaches demonstrate a role for T-type channels in melanoma viability and proliferation. These results encourage the analysis of T-type VGCCs as targets for therapeutic intervention in melanoma tumorigenesis and/or tumour progression.
电压门控钙通道（VGCCs）的表达在黑色素瘤细胞中尚未有报道，尽管越来越多的证据表明 VGCCs 在肿瘤发生和肿瘤进展中起作用。为了解决这个问题，我们对人黑色素细胞和一系列黑色素瘤细胞系和活检样本中的 VGCC 表达进行了广泛的 RT-PCR 分析。此外，我们使用 Ca(2+)成像技术测试了这些通道的功能表达，并研究了它们与黑色素瘤细胞活力和增殖的相关性。我们的结果表明，对照黑色素细胞和黑色素瘤细胞表达属于 Ca(v) 1 和 Ca(v) 2 基因家族的通道亚型。重要的是，低电压激活的 Ca(v) 3（T 型）通道的表达仅限于黑色素瘤。我们已经证实 T 型通道作为黑色素瘤细胞中组成型 Ca(2+)内流的介质的功能。最后，药理学和基因沉默方法表明 T 型通道在黑色素瘤活力和增殖中起作用。这些结果鼓励分析 T 型 VGCCs 作为治疗干预黑色素瘤肿瘤发生和/或肿瘤进展的靶点。
