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Research Articles: Therapeutics, Targets, and Development

Identification of SK3 channel as a new mediator of breast cancer cell migration

¹ Inserm E 211, Nutrition, Croissance et Cancer and Université François Rabelais, Tours, France and ² FRE 2939-Centre National de la Recherche Scientifique, Génomes et Cancers, Institut Gustave Roussy, Villejuif, France

Requests for reprints: Christophe Vandier, Inserm E-0211, Nutrition Croissance et Cancer, University Francois Rabelais, 10 boulevard Tonnelle, Tours, F-37000 France. Phone: 33-2-4736-6024; Fax: 33-2-4736-6226. E-mail: christophe.vandier{at}univ-tours.fr

Abstract

Potassium channels have been involved in epithelial tumorigenesis but the role of small-conductance Ca²⁺-activated K⁺ channels is unknown. We report here that small-conductance Ca²⁺-activated K⁺ channels are expressed in a highly metastasizing mammary cancer cell line, MDA-MB-435s. Patch-clamp recordings showed typical small-conductance Ca²⁺-activated K⁺ channel–mediated currents sensitive to apamin, 4-aminopyridine, and tetraethylammonium. Moreover, the cells displayed a high intracellular calcium concentration, which was decreased after 24 hours of apamin treatment. By regulating membrane potential and intracellular calcium concentration, these channels were involved in MDA-MB-435s cell migration, but not in proliferation. Only SK3 protein expression was observed in these cells in contrast to SK2, which was expressed both in cancer and noncancer cell lines. Whereas small interfering RNA directed against SK3 almost totally abolished MDA-MB-435s cell migration, transient expression of SK3 increased migration of the SK3-deficient cell lines, MCF-7 and 184A1. SK3 channel was solely expressed in tumor breast biopsies and not in nontumor breast tissues. Thus, SK3 protein channel seems to be a new mediator of breast cancer cell migration and represents a potential target for a new class of anticancer agents. [Mol Cancer Ther 2006;5(11):2946–53]

Grant support: "Ligue contre le Cancer-Région Centre," "Fondation Carrefour," "Institut National de la Sante et de la Recherche Medicale," and "Cancéropole Grand Ouest"; and fellowships from the "Ligue contre le Cancer" (M. Potier) and the "Ministère de la Recherche et de la Technologie" (S. Roger).

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.

Received 4/10/06; revised 7/26/06; accepted 9/11/06.

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