Ca2+-activated K+ channels in human melanoma cells are up-regulated by hypoxia involving hypoxia-inducible factor-1alpha and the von Hippel-Lindau protein.
Ca2+-activated K+ channels in human melanoma cells are up-regulated by hypoxia involving hypoxia-inducible factor-1alpha and the von Hippel-Lindau protein.
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DOI：
10.14849/psjproc.2007.0_220_2
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
Nobuyoshi Tajima;K. Schönherr;Susanna Niedling;M. Kaatz;H. Kanno;R. Schönherr;S. Heinemann
中科院分区：
文献类型：
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作者：
Nobuyoshi Tajima;K. Schönherr;Susanna Niedling;M. Kaatz;H. Kanno;R. Schönherr;S. Heinemann
在慢性缺氧下，肿瘤细胞经历涉及缺氧诱导因子（HIF）的适应性变化。在这里，我们报告的离子电流介导的钙激活的K+（K（Ca））通道在人黑色素瘤IGR 1细胞增加慢性缺氧（3%O2），以及缺氧模拟。这种增加涉及HIF系统，如通过HIF-1 α或von Hippel-Lindau肿瘤抑制基因的过表达所证实的。在常氧条件下，IGR 1细胞中的K（Ca）通道显示出中间电导K（Ca）亚型IK通道的药理学特征，而亚型SK 2通道在缺氧下上调，显示与药理学工具和mRNA分析。缺氧增加细胞增殖，但K（Ca）通道阻断剂apamin和charybdotoxin减慢细胞生长，特别是在缺氧条件下。对于细胞系IGR 39和从黑素瘤转移的活组织检查中急性分离的细胞获得了类似的结果。因此，上调的K（Ca）通道可能是一种新的机制，其中HIF可以有助于人类肿瘤细胞的恶性表型。
Under chronic hypoxia, tumour cells undergo adaptive changes involving hypoxia-inducible factors (HIFs). Here we report that ion currents mediated by Ca2+-activated K+ (K(Ca)) channels in human melanoma IGR1 cells are increased by chronic hypoxia (3% O2), as well as by hypoxia mimetics. This increase involves the HIF system as confirmed by overexpression of HIF-1alpha or the von Hippel-Lindau tumour suppressor gene. Under normoxic conditions the K(Ca) channels in IGR1 cells showed pharmacological characteristics of intermediate conductance K(Ca) subtype IK channels, whereas the subtype SK2 channels were up-regulated under hypoxia, shown with pharmacological tools and with mRNA analysis. Hypoxia increased cell proliferation, but the K(Ca) channel blockers apamin and charybdotoxin slowed down cell growth, particularly under hypoxic conditions. Similar results were obtained for the cell line IGR39 and for acutely isolated cells from a biopsy of a melanoma metastasis. Thus, up-regulation of K(Ca) channels may be a novel mechanism by which HIFs can contribute to the malignant phenotype of human tumour cells.