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TREK-1 Is a Novel Molecular Target in Prostate Cancer

Departments of ¹ Pharmacology, ² Pathology, and ³ Medicine, ⁴ Irving Comprehensive Cancer Center; and ⁵ Center for Molecular Therapeutics, Columbia University Medical Center, New York, New York

Requests for reprints: Steven J. Feinmark, Department of Pharmacology, 630 West 168th Street, New York, NY 10032. Phone: 212-305-3567; Fax: 212-305-4741; E-mail: sjf1{at}columbia.edu.

Key Words: TREK-1 • proliferation • prostate cancer • potassium channel • K_2P channel

TREK-1 is a two-pore domain (K_2P) potassium channel that carries a leak current that is time- and voltage-independent. Recently, potassium channels have been related to cell proliferation and some K_2P family channels, such as TASK-3, have been shown to be overexpressed in specific neoplasms. In this study, we addressed the expression of TREK-1 in prostatic tissues and cell lines, and we have found that this potassium channel is highly expressed in prostate cancer but is not expressed in normal prostate nor in benign prostatic hyperplasia. Furthermore, expression of TREK-1 correlates strongly with the grade and the stage of the disease, suggesting a causal link between channel expression and abnormal cell proliferation. In vitro studies showed that TREK-1 is highly expressed in PC3 and LNCaP prostate cancer cell lines but is not detectable in normal prostate epithelial cells (NPE). In this report, we show that overexpression of TREK-1 in NPE and Chinese hamster ovary (CHO) cells leads to a significant increase in proliferation. Moreover, the increased cell proliferation rate of PC3 cells and TREK-1 overexpressing CHO cells could be reduced when TREK-1 current was reduced by overexpression of a dominant-negative TREK-1 mutant or when cells were exposed to a TREK-1 inhibitor. Taken together, these data suggest that TREK-1 expression is associated with abnormal cell proliferation and may be a novel marker for and a molecular target in prostate cancer. [Cancer Res 2008;68(4):1197–203]