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J. Biol. Chem., Vol. 283, Issue 12, 7421-7428, March 21, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/12/7421    most recent M703758200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Spitzner, M. Articles by Kunzelmann, K. PubMed PubMed Citation Articles by Spitzner, M. Articles by Kunzelmann, K. Social Bookmarking                      What's this?

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.

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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