TY - JOUR
T1 - Eag1 and bestrophin 1 are up-regulated in fast-growing colonic cancer cells
AU - Spitzner, Melanie
AU - Martins, Joana Raquel
AU - Soria, René Barro
AU - Ousingsawat, Jiraporn
AU - Scheidt, Kerstin
AU - Schreiber, Rainer
AU - Kunzelmann, Karl
PY - 2008/3/21
Y1 - 2008/3/21
N2 - Ion channels like voltage-gated ether-á-go-go (Eag1) K+ channels or Ca2+-activated Cl- channels have been shown to support cell proliferation. Bestrophin 1 (Best1) has been proposed to form Ca2+-activated Cl- channels in epithelial cells. Here we show that original T84 colonic carcinoma cells grow slowly (T 84-slow) and express low amounts of Eag1 and Best1, whereas spontaneously transformed T84 cells grow fast (T84-fast) and express high levels of both proteins. Both Eag1 and Best1 currents are up-regulated in T84-fast cells. Eag1 currents were cell cycle-dependent with up-regulation during G1/S transition. T 84-slow, but not T84-fast, cells formed tight monolayers when grown on permeable supports. RNA interference inhibition of Eag1 and Best1 reduced proliferation of T84-fast cells, whereas overexpression of Best1 turned T84-slow into fast-growing cells. Eag1 and Best1 improve intracellular Ca2+ signaling and cell volume regulation. These results establish a novel role for bestrophins in cell proliferation.
AB - Ion channels like voltage-gated ether-á-go-go (Eag1) K+ channels or Ca2+-activated Cl- channels have been shown to support cell proliferation. Bestrophin 1 (Best1) has been proposed to form Ca2+-activated Cl- channels in epithelial cells. Here we show that original T84 colonic carcinoma cells grow slowly (T 84-slow) and express low amounts of Eag1 and Best1, whereas spontaneously transformed T84 cells grow fast (T84-fast) and express high levels of both proteins. Both Eag1 and Best1 currents are up-regulated in T84-fast cells. Eag1 currents were cell cycle-dependent with up-regulation during G1/S transition. T 84-slow, but not T84-fast, cells formed tight monolayers when grown on permeable supports. RNA interference inhibition of Eag1 and Best1 reduced proliferation of T84-fast cells, whereas overexpression of Best1 turned T84-slow into fast-growing cells. Eag1 and Best1 improve intracellular Ca2+ signaling and cell volume regulation. These results establish a novel role for bestrophins in cell proliferation.
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U2 - 10.1074/jbc.M703758200
DO - 10.1074/jbc.M703758200
M3 - Article
C2 - 18222922
AN - SCOPUS:43149104771
VL - 283
SP - 7421
EP - 7428
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 12
ER -