HERG K+ channel, a regulator of tumor cell apoptosis and proliferation.

Wang, Huizhen; Zhang, Yiqiang; Cao, Liwen; Han, Hong; Wang, Jingxiong; Yang, Baofeng; Nattel, Stanley; Wang, Zhiguo · Cancer Res · 2002

basic_science · Level V

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Abstract

The human ether-a-go-go related gene (HERG) encodes K+ channel identified as a molecular target for mutations underlying some forms of the long Q-T syndrome, a lethal cardiac arrhythmia. Recent studies revealed that HERG is abundantly expressed in a variety of tumor cells. Yet, the role of HERG in tumor cells had remained unclear. Here, we show that HERG conductance markedly promotes H2O2-induced apoptosis of various tumor cells, whereas HERG expression facilitates the tumor cell proliferation caused by tumor necrosis factor (TNF) ligand (TNF-alpha). Immunostaining and immunocoprecipitation reveal coexpression of HERG and TNF receptor 1 on the cytoplasmic membrane, which is correlated with greater activities of nuclear transcription factor, nuclear factor-kappaB, in HERG-expressing tumor cells. Our data suggest that HERG K+ channel is a regulator of tumor cell proliferation and apoptosis and provide a potential new target for cancer therapy.

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