Reduction of breast cancer cell migration via up-regulation of TASK-3 two-pore domain K plus channel
Reduction of breast cancer cell migration via up-regulation of TASK-3 two-pore domain K plus channel
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DOI：
10.1111/j.1748-1716.2011.02359.x
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发表时间：
2012-04-01
影响因子：
6.3
通讯作者：
Kang, D.
中科院分区：
文献类型：
--
作者：
Lee, G-W.;Park, H. S.;Kang, D.
目的：多种K+通道在多种细胞中表达，包括癌细胞。然而，只有少量的研究探讨了电压非依赖性K+通道与乳腺癌之间的关系。本研究旨在探讨双孔结构域钾离子通道（K2P）表达水平的变化是否与人乳腺癌细胞的迁移有关。K2P通道基因/蛋白表达水平在MCF-7和MCF-7之间进行了比较。（非侵入性细胞）和MDA-MB-231（一种侵袭性细胞）进行逆转录酶（RT）-聚合酶链反应（PCR）、实时PCR、蛋白质印迹和免疫细胞化学。K2P通道表达水平和细胞迁移之间的关系进行了分析，使用基因过表达和敲低技术。结果：与MDA-MB-231细胞相比，K2P通道中，TASK3在MCF-7细胞中的mRNA和蛋白表达量明显增加。乳腺癌细胞中过表达的ASK-3减少了迁移和侵袭，而沉默的ASK-3增加了迁移和侵袭。PKC激活剂佛波醇肉豆蔻酸酯（PMA）可降低ASK-3的表达水平。结论：乳腺癌细胞中，MAPK-3表达水平的升高可通过PKC的激活而被调节，从而降低了细胞的迁移/侵袭能力，提示通过调节MAPK-3的表达，可调节乳腺癌细胞的转移。
Aim: Many kinds of K+ channels are expressed in a variety of cells, including cancer cells. However, only a small amount of research has explored the relationship between voltage-independent K+ channels and breast cancer. This study was performed to investigate whether changes in two-pore domain K+ (K2P) channel expression levels are related to the migration of human breast cancer cells.Methods: K2P channel gene/ protein expression levels were compared between MCF-7 (a non-invasive cell) and MDA-MB-231 (an invasive cell) using reverse transcriptase (RT)-polymerase chain reaction (PCR), real-time PCR, Western blotting and immunocytochemistry. The relationship between K2P channel expression level and cell migration was analysed using gene overexpression and knock-down techniques. Functional expression of TASK3 in MCF-7 and MDA-MB-231 cells was recorded using patch-clamp technique.Results: Of K2P channels, TASK-3 mRNA and protein were highly expressed in MCF-7 cells compared with those in MDA-MB-231 cells. Overexpression of TASK-3 in breast cancer cells reduced migration and invasion, whereas silencing of TASK-3 increased the migration and invasion. The TASK-3 expression level was decreased by phorbol myristate acetate (PMA), a PKC activator. PMA also enhanced the cell migration in MDAMB- 231 cells.Conclusion: These results show that an increase in TASK-3 expression levels, which could be modulated by PKC activation, reduces cell migration/ invasion in breast cancer cells and suggest that modulation of TASK-3 expression may regulate metastasis of breast cancer cells.