Suzuki Takahiro, Takimoto Koichi
Department of Environmental and Occupational Health, Graduate School of Pulic Health, University of Pittsburgh, PA 15260, USA.
Int J Oncol. 2004 Jul;25(1):153-9.
Voltage-gated potassium (Kv) channels play important roles in differentiation and growth of non-excitable cells. Inhibition of these channels is also known to suppress proliferation of various cancer cells. Here we examine expression of K+ channel subunit genes in various uterine cancer cells and their roles in cell proliferation. RT-PCR analysis reveals that cervical squamous cell carcinoma (C-33A, MS-751 and QG-U), and endometrial adenocarcinoma (AN3-CA, KLE and Ishikawa), but not cervical adenocarcinoma (CAC-1 and OMC-4), expresses both or either one of the two human eag-related genes (HERG2 and 3, or KCNH6 and 7). In addition, mRNAs for one-transmembrane auxiliary subunits (KCNE1-3) are significant in these cells. Moreover, the two cervical adenocarcinoma cell lines, as well as some of the squamous and endometrial cancer cell lines, express mRNAs for Kv2.1 and the silent regulatory subunit for Kv2.1 channels, Kv9.3. Thus, squamous/endometrial cancer cells contain HERG-KCNE channel complexes, whereas Kv2.1-Kv9.3 channels may be major components of Kv channels in cervical adenocarcinoma cells. To evaluate the involvement of these channels in cell proliferation, we used the specific blockers for HERG and Kv2.1-containing channels, E-4031 and hanatoxin-1. E-4031 significantly reduced proliferation of C-33A, MS-751 and QG-U by 15-30%. Similarly, hanatoxin-1 suppressed growth of Kv2.x-expressing cells (25-40%). Finally, FACS analysis indicates that inhibition of HERG channels reduces a population of cells in the G2/M phase. These results suggest that HERG-KCNE and Kv2.1-Kv9.3 channels are selectively involved in proliferation of distinct uterine cancer cells.
电压门控钾（Kv）通道在非兴奋性细胞的分化和生长中发挥着重要作用。已知抑制这些通道也能抑制各种癌细胞的增殖。在此，我们研究了钾离子通道亚基基因在各种子宫癌细胞中的表达及其在细胞增殖中的作用。逆转录聚合酶链反应（RT-PCR）分析显示，宫颈鳞状细胞癌（C-33A、MS-751和QG-U）以及子宫内膜腺癌（AN3-CA、KLE和Ishikawa），而非宫颈腺癌（CAC-1和OMC-4），表达两个人类醚-去极化相关基因（HERG2和3，或KCNH6和7）中的一个或两个。此外，单跨膜辅助亚基（KCNE1-3）的信使核糖核酸在这些细胞中含量显著。此外，两种宫颈腺癌细胞系以及一些鳞状和子宫内膜癌细胞系表达Kv2.1的信使核糖核酸以及Kv2.1通道的沉默调节亚基Kv9.3。因此，鳞状/子宫内膜癌细胞含有HERG-KCNE通道复合物，而Kv2.1-Kv9.3通道可能是宫颈腺癌细胞中钾离子通道的主要成分。为了评估这些通道在细胞增殖中的作用，我们使用了HERG和含Kv2.1通道的特异性阻滞剂E-4031和芋螺毒素-1。E-4031显著降低了C-33A、MS-751和QG-U的增殖，降幅为15%-30%。同样，芋螺毒素-1抑制了表达Kv2.x的细胞的生长（25%-40%）。最后，荧光激活细胞分选（FACS）分析表明，抑制HERG通道会减少处于G2/M期的细胞群体。这些结果表明，HERG-KCNE和Kv2.1-Kv9.3通道选择性地参与了不同子宫癌细胞的增殖。
