Eag1 and bestrophin 1 are up-regulated in fast-growing colonic cancer cells

Ion channels like voltage-gated ether-a-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 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 G1/ 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 Ca2+ signaling and cell volume regulation. These results establish a novel role for bestrophins in cell proliferation.