Suppression of transient receptor potential melastatin 7 channel induces cell death in gastric cancer

Ca2+ and Mg2+ have a fundamental role in many cellular processes and ion channels are involved in normal physiologic processes and in the pathology of various diseases. The aim here was to show that the presence and potential role of transient receptor potential melastatin 7 (TRPM7) channels in the growth and survival of AGS cells, the most common human gastric adenocarcinoma cell line. The patch-clamp technique for whole-cell recording was used in AGS cells. TRPM7-specific small interfering RNAs were used for specific inhibition of TRPM7. Whole-cell voltage-clamp recordings revealed the TRPM7-like currents that activated spontaneously following loss of intracellular Mg2+. The current had a non-linear current-voltage relationship with the characteristic steep outward rectification associated with TRPM7 channels. Reverse transcription-polymerase chain reaction, western blotting, and immunoreactivity all showed abundant expression of TRPM7 messenger RNA and protein in AGS cells. Transfection of AGS cells with TRPM7 siRNA significantly reduced the expression of TRPM7 mRNA and protein as well as the amplitude of the TRPM7-like currents. Furthermore, we found that Mg2+ is critical for the growth and survival in AGS cells. Blockade of TRPM7 channels by La3+ and 2-APB or suppression of TRPM7 expression by siRNA inhibited the growth and survival of these cells. Human gastric adenocarcinoma cells express TRPM7 channel whose presence is essential for cell survival. The protein is a likely potential target for the pharmacological treatment of gastric cancer. (Cancer Sci 2008; 99: 2502-2509).