Identification of SK3 channel as a new mediator of breast cancer cell migration
Identification of SK3 channel as a new mediator of breast cancer cell migration
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DOI：
10.1158/1535-7163.mct-06-0194
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发表时间：
2006-11-01
影响因子：
5.7
通讯作者：
Vandier, Christophe
中科院分区：
文献类型：
--
作者：
Potier, Marie;Joulin, Virginie;Vandier, Christophe
钾通道参与上皮肿瘤的发生，但小电导钙激活的钾通道的作用是未知的。我们在这里报告，小电导Ca 2+激活的K+通道表达在一个高度转移的乳腺癌细胞系，MDA-MB-435 s。膜片钳记录显示典型的小电导钙激活的K+通道介导的电流敏感的apamin，4-氨基吡啶，和四乙铵。此外，细胞显示出高的细胞内钙浓度，其在apamin处理24小时后降低。通过调节膜电位和细胞内钙离子浓度，这些通道参与MDA-MB 435 s细胞迁移，但不参与增殖。在这些细胞中仅观察到SK 3蛋白表达，而SK2在癌细胞和非癌细胞系中均表达。而针对SK 3的小干扰RNA几乎完全消除了MDA-MB 435细胞迁移，SK 3的瞬时表达增加了SK 3缺陷细胞系MCF-7和184 A1的迁移。SK 3通道仅在肿瘤乳腺活检组织中表达，而在非肿瘤乳腺组织中不表达。因此，SK 3蛋白通道似乎是乳腺癌细胞迁移的新介质，并代表了一类新型抗癌药物的潜在靶点。
Potassium channels have been involved in epithelial tumorigenesis but the role of small-conductance Ca2+-activated K+ channels is unknown. We report here that small-conductance Ca2+-activated K+ channels are expressed in a highly metastasizing mammary cancer cell line, MDA-MB-435s. Patch-clamp recordings showed typical small-conductance Ca2+-activated K+-channel-mediated currents sensitive to apamin, 4-aminopyridine, and tetraethylammonium. Moreover, the cells displayed a high intracellular calcium concentration, which was decreased after 24 hours of apamin treatment. By regulating membrane potential and intracellular calcium concentration, these channels were involved in MDA-MB435s cell migration, but not in proliferation. Only SK3 protein expression was observed in these cells in contrast to SK2, which was expressed both in cancer and noncancer cell lines. Whereas small interfering RNA directed against SK3 almost totally abolished MDA-MB435s cell migration, transient expression of SK3 increased migration of the SK3-deficient cell lines, MCF-7 and 184A1. SK3 channel was solely expressed in tumor breast biopsies and not in nontumor breast tissues. Thus, SK3 protein channel seems to be a new mediator of breast cancer cell migration and represents a potential target for a new class of anticancer agents.