| Sumario: | Ether-a´-go-go-1 (Eag1) is a CNS-localized voltage-gated potassium channel that is found ectopically expressed in a majority of extracranial solid tumors. While circumstantial evi dence linking Eag1 to tumor biology has been well established, the mechanisms by which the channel contributes to tumor pro gression remain elusive. In this study, we have used in vivo and in vitro techniques to identify a candidate mechanism. A muta tion that eliminates ion permeation fails to completely abolish xenograft tumor formation by transfected cells, indicating that Eag1 contributes to tumor progression independently of its pri mary function as an ion channel. Our data suggest that Eag1 interferes with the cellular mechanism for maintaining oxygen homeostasis, increasing HIF-1 activity, and thereby VEGF secretion and tumor vascularization
|
|---|
