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 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.