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J. Biol. Chem., Vol. 283, Issue 12, 7421-7428, March 21, 2008
Eag1 and Bestrophin 1 Are Up-regulated in Fast-growing Colonic Cancer Cells*From the Institut für Physiologie, Universität Regensburg, Universitätsstrasse 31, D-93053 Regensburg, Germany 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 (T84-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. T84-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.
Received for publication, May 7, 2007 , and in revised form, December 31, 2007. * This work was supported by Deutsche Forschungsgemeinschaft Grant SFB699 A7 and the Else-Kröner-Fresenius-Stiftung. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 Both authors contributed equally to this work. 2 To whom correspondence should be addressed. Tel.: 49-954-4302; Fax: 49-941-4315; E-mail: uqkkunze{at}mailbox.uq.edu.
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