Voltage-Gated Potassium Channels Take Part in the Early Transformation and Oncogenesis of Breast Cancer

【摘要】：正Potassium channels(K~+ channel) are membrane-spanning proteins that selectively conduct K ions across the cell membrane along its electrochemical gradient,and are involved in many physiological functions. Voltage-Gated Potassium Channels(Kv) are widely expressed in several kinds of cells where they play the essential role in membrane potential.Additionally,the targeting of Kv channels to cholesterol-rich membrane micro -domains has emerged as a novel mechanism of ion channel localization.However, few studies have reported the Kv channel expression in mammary cells.The purpose of this study was to investigate the role of Kv in the tumor early transformation and oncogenesis. Here,the expressions of Kv1.1,Kv1.2, Kv1.3,and Kv1.5 were tested in normal human mammary epithelial cells(MCF10A, MCF10A-ST1) and breast cancer cell MCF-7 by Western Blot and RT-PCR.The relationship of Kv1.5 and Caveolin-1(Cav-1) in MCF10A cell by immuno-precipitation was also investigated.In addition,after using 4- AP,which can specially block Kv channels, the activities of MAPK pathway were detected in MCF10A and MCF10A-ST1 cells,while contrasted with MCF-7 cells.Data showed, firstly,that different Kv channels have different expressions in MCF10A,MCF10A-ST1 and MCF-7 cells and also that the expression of Kv1.5 was related with Cav-1;secondly, activation of MAPK pathways were not the same in the afore-mentioned cells after blocking the voltage-gated K~+ current;thirdly, improving the expression of Kv1.5 in MCF-7 cells might enhance the Cav-1 expression and activate MAPK pathways.When viewed together, the data demonstrates that,Kv1.5 is related with Cav-1 in mammary cells,and might contribute to the early transformation and oncogenesis of breast cancer.