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.