Eag1 and Bestrophin 1 are up-regulated in fast-growing colonic cancer cells.
Ion channels like voltage-gated ether-á-go-go (Eag1) K(+) channels or Ca(2+)-activated Cl(-) channels have been shown to support cell proliferation. Bestrophin 1 (Best1) has been proposed to form Ca(2+)-activated Cl(-) channels in epithelial cells. Here we show that original T(84) colonic carcinoma cells grow slowly (T(84)-slow) and express low amounts of Eag1 and Best1, whereas spontaneously transformed T(84) cells grow fast (T(84)-fast) and express high levels of both proteins. Both Eag1 and Best1 currents are up-regulated in T(84)-fast cells. Eag1 currents were cell cycle-dependent with up-regulation during G(1)/S transition. T(84)-slow, but not T(84)-fast, cells formed tight monolayers when grown on permeable supports. RNA interference inhibition of Eag1 and Best1 reduced proliferation of T(84)-fast cells, whereas overexpression of Best1 turned T(84)-slow into fast-growing cells. Eag1 and Best1 improve intracellular Ca(2+) signaling and cell volume regulation. These results establish a novel role for bestrophins in cell proliferation.
Spitzner
Melanie
M
Institut für Physiologie, Universität Regensburg, Universitätsstrasse 31, D-93053 Regensburg, Germany.
Martins
Joana Raquel
JR
Soria
René Barro
RB
Ousingsawat
Jiraporn
J
Scheidt
Kerstin
K
Schreiber
Rainer
R
Kunzelmann
Karl
K
D000075002:Bestrophins; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D048429:Cell Size; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D005136:Eye Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016193:G1 Phase / Q000502:physiology*; D006801:Humans; D034622:RNA Interference; D016196:S Phase / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D051638:Ether-A-Go-Go Potassium Channels; D005136:Eye Proteins; C496884:KCNH1 protein, human