HERG K+ Channel, a Regulator of Tumor Cell Apoptosis and Proliferation

H Wang, Y Zhang, L Cao, H Han, J Wang, B Yang… - Cancer research, 2002 - AACR
H Wang, Y Zhang, L Cao, H Han, J Wang, B Yang, S Nattel, Z Wang
Cancer research, 2002AACR
The human ether-a-go-go related gene (HERG) encodes K+ channel identifiedas a
molecular target for mutations underlying some forms of thelong QT 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 …
Abstract
The human ether-a-go-go related gene (HERG) encodes K+ channel identifiedas a molecular target for mutations underlying some forms of thelong 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-α). 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-κB, 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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