Expression of delayed rectifier potassium channels and their possible roles in proliferation of human gastric cancer cells

Voltage-gated potassium (Kv) channels have been reported to be involved in the proliferation of many types of cells, including tumor cells. The overexpression of the Kv channels and related channel activity are involved in the neoplastic process. Our previous study has shown the existence of delayed rectifier potassium (IK) current in gastric cancer cells SGC7901. However, the expression and function of most delayed rectifier potassium (KD) channel subunits in gastric cancer cells are not completely resolved. Here we examine expression of KD channel subunits in Kv1-Kv3 families in immortalized gastric epithelial cells GES and various gastric cancer cells (including AGS, KATO¢Û, MKN28, MKN45, MGC803, SGC7901, SGC7901/ADR, and SGC7901/VCR), and their roles in cell proliferation. RT-PCR analysis reveals that all cell lines examined express Kv1.3, Kv1.5, Kv1.6, Kv2.1, and Kv2.2. However, Kv1.2 and Kv3.2 genes are barely detectable in any given cancer cell lines. Kv1.5 protein, high mRNA levels in all cell lines examined, is also expressed in some cancer cells lines and more frequently detected in gastric cancer tissues. Down-regulation of the expression of Kv1.5 in SGC7901 with RNA interference significantly inhibited the proliferation and tumorigenicity of SGC7901 cells. Moreover, in Ca2+-containing rather than Ca2+-free medium, KCl (50mM) stimulated a rapid increase in the concentration of cytosolic calcium in empty vector transfected cells that was blocked by verapamil. Likewise, decrease the expression of Kv1.5 with short interfering RNA also blocked the depolarization-induced influx of Ca2+. This finding suggests that more than one kind of KD channel subunits are expressed in various gastric cancer cell lines. Kv1.5 may involved in tumor cells proliferation by controlling Ca2+ entry, and the interference of KD channels expression and/or activity could provide a novel strategy to reverse the malignant phenotype of gastric cancer cells.