HERG K+ channel, a regulator of tumor cell apoptosis and proliferation.
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.
Department of Medicine, Montreal Heart Institute, University of Montreal, Montreal, Quebec, H1T 1C8 Canada.
Huizhen
H
Wang
Yiqiang
Y
Zhang
Liwen
L
Cao
Hong
H
Han
Jingxiong
J
Wang
Baofeng
B
Yang
Stanley
S
Nattel
Zhiguo
Z
Wang
D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D027682:Cation Transport Proteins; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006338:Heart Neoplasms / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015674:Mammary Neoplasms, Animal / Q000473:pathology; D009369:Neoplasms / Q000473:pathology*; D009447:Neuroblastoma / Q000473:pathology; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014407:Tumor Cells, Cultured
D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D006861:Hydrogen Peroxide