Suppression of transient receptor potential melastatin 7 channel induces cell death in gastric cancer
2008-11-20 10:46:11 조회수515
Byung Joo Kim, Eun Jung Park, Jae Hwa Lee, Ju-Hong Jeon, Seon Jeong Kim, Insuk So Center for Bio-Artificial Muscle and Department of Biomedical Engineering, Hanyang University, Seoul 133-791, Korea 원문 링크 :


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)

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