Reduction of breast cancer cell migration via up-regulation of TASK ...

Lee GW, Park HS, Kim EJ, Cho YW, Kim GT, Mun YJ, Choi EJ, Lee JS, Han J, Kang D.

Acta Physiol (Oxf). 2012 Apr;204(4):513-24.

Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, South Korea.

Abstract

AIM:

Many kinds of K(+) channels are expressed in a variety of cells, including cancer cells. However, only a small amount of research has explored the relationship between voltage-independent K(+) channels and breast cancer. This study was performed to investigate whether changes in two-pore domain K(+) (K(2P) ) channel expression levels are related to the migration of human breast cancer cells.

METHODS:

K(2P) channel gene/protein expression levels were compared between MCF-7 (a non-invasive cell) and MDA-MB-231 (an invasive cell) using reverse transcriptase (RT)-polymerase chain reaction (PCR), real-time PCR, Western blotting and immunocytochemistry. The relationship between K(2P) channel expression level and cell migration was analysed using gene overexpression and knock-down techniques. Functional expression of TASK-3 in MCF-7 and MDA-MB-231 cells was recorded using patch-clamp technique.

RESULTS:

Of K(2P) channels, TASK-3 mRNA and protein were highly expressed in MCF-7 cells compared with those in MDA-MB-231 cells. Overexpression of TASK-3 in breast cancer cells reduced migration and invasion, whereas silencing of TASK-3 increased the migration and invasion. The TASK-3 expression level was decreased by phorbol myristate acetate (PMA), a PKC activator. PMA also enhanced the cell migration in MDA-MB-231 cells.

CONCLUSION:

These results show that an increase in TASK-3 expression levels, which could be modulated by PKC activation, reduces cell migration/invasion in breast cancer cells and suggest that modulation of TASK-3 expression may regulate metastasis of breast cancer cells.

? 2011 The Authors. Acta Physiologica ? 2011 Scandinavian Physiological Society.

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