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

Cited 95 time in Web of Science Cited 93 time in Scopus
Authors
Kim, Byung Joo; Park, Eun Jung; Lee, Jae Hwa; Jeon, Ju-Hong; Kim, Seon Jeong; So, Insuk
Issue Date
2008-11-27
Publisher
Wiley-Blackwell
Citation
Cancer Sci. 2008; 99(12): 2502-2509
Keywords
Adenocarcinoma/genetics/pathologyCaspase 3/analysis/metabolismCell Death/geneticsCell Line, TumorElectrophysiologyFormazans/analysis/metabolismHumansImmunohistochemistryPatch-Clamp TechniquesRNA InterferenceRNA, Messenger/metabolismRNA, Small Interfering/metabolismStomach Neoplasms/*genetics/pathologyTRPM Cation Channels/*antagonists & inhibitors/*geneticsTetrazolium Salts/analysis/metabolismZinc Fingers/*genetics
Abstract
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.
ISSN
1349-7006 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19032368

http://hdl.handle.net/10371/68149
DOI
https://doi.org/10.1111/j.1349-7006.2008.00982.x
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Physiology (생리학교실)Journal Papers (저널논문_생리학교실)
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