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Blockage of intermediate-conductance-Ca2+-activated K+ channels inhibits progression of human endometrial cancer

Abstract

Potassium (K+) channels have been implicated in proliferation of some tumor cells. However, whether K+ channels are important to the pathogenesis of endometrial cancer (EC) remains unknown. In the present study, we report that intermediate-conductance Ca2+-activated K+ (IKCa1) channels play a critical role in the development of EC. The expression of IKCa1 at both mRNA and protein levels in EC tissues was greatly increased than that in atypical hyperplasia and normal tissues. Treatment of EC cells with clotrimazole and TRAM-34, two agents known to inhibit IKCa1 channels, suppressed the proliferation of EC cells and blocked EC cell cycle at G0/G1 phase. Similarly, downregulation of IKCa1 by siRNA against IKCa1 inhibited EC cell proliferation and arrested its cell cycle at G0/G1 phase. A clotrimazole-sensitive K+ current was induced in EC cells in response to the increased Ca2+. The current density induced by Ca2+ was greatly reduced by clotrimazole, TRAM-34, charybdotoxin or downregulation of IKCa1 by the siRNA against IKCa1. Furthermore, TRAM-34 and clotrimazole slowed the formation in nude mice of tumor generated by injection of EC cells. Our results suggest that increased activity of IKCa1 channel is necessary for the development of EC.

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Acknowledgements

This work was supported by grants from the Shanghai government (05-III-16), the health bureau technology development fund of Shanghai (054003), the 973 program (2006CB806600 and 2006CB504700) and project 30225025 from the NNSF of China.

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Correspondence to Y J Feng or Y Z Wang.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Wang, Z., Shen, B., Yao, H. et al. Blockage of intermediate-conductance-Ca2+-activated K+ channels inhibits progression of human endometrial cancer. Oncogene 26, 5107–5114 (2007). https://doi.org/10.1038/sj.onc.1210308

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