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.

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