NDLI: Increase in Serum $Ca^{2+/}Mg^{2+}$ Ratio Promotes Proliferation of Prostate Cancer Cells by Activating TRPM7 $Channels^{*}$

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Increase in Serum $Ca^{2+/}Mg^{2+}$ Ratio Promotes Proliferation of Prostate Cancer Cells by Activating TRPM7 $Channels^{*}$

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sahmoun, Abe E. Selvaraj, Senthil Derry, Susan Sun, Yuyang Varma, Archana Singh, Brij B.
Description	Author Affiliation: Sun Y ( Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, North Dakota 58201, USA.)
Abstract	TRPM7 is a novel magnesium-nucleotide-regulated metal current (MagNuM) channel that is regulated by serum $Mg^{2+}$ concentrations. Changes in $Mg^{2+}$ concentration have been shown to alter cell proliferation in various cells; however, the mechanism and the ion channel(s) involved have not yet been identified. Here we demonstrate that TRPM7 is expressed in control and prostate cancer cells. Supplementation of intracellular Mg-ATP or addition of external 2-aminoethoxydiphenyl borate inhibited MagNuM currents. Furthermore, silencing of TRPM7 inhibited whereas overexpression of TRPM7 increased endogenous MagNuM currents, suggesting that these currents are dependent on TRPM7. Importantly, although an increase in the serum $Ca^{2+}/Mg^{2+}$ ratio facilitated $Ca^{2+}$ influx in both control and prostate cancer cells, a significantly higher $Ca^{2+}$ influx was observed in prostate cancer cells. TRPM7 expression was also increased in cancer cells, but its expression was not dependent on the $Ca^{2+}/Mg^{2+}$ ratio per se. Additionally, an increase in the extracellular $Ca^{2+}/Mg^{2+}$ ratio led to a significant increase in cell proliferation of prostate cancer cells when compared with control cells. Consistent with these results, age-matched prostate cancer patients also showed a subsequent increase in the $Ca^{2+}/Mg^{2+}$ ratio and TRPM7 expression. Altogether, we provide evidence that the TRPM7 channel has an important role in prostate cancer and have identified that the $Ca^{2+}/Mg^{2+}$ ratio could be essential for the initiation/progression of prostate cancer.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	1
Volume Number	288
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2013-01-04
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Calcium Chemistry Gene Expression Regulation, Neoplastic Magnesium Prostatic Neoplasms Metabolism TRPM Cation Channels Calcium Signaling Cell Line, Tumor Cell Proliferation Cell Survival Electrophysiology Ions Microscopy, Confocal Patch-Clamp Techniques Protein-Serine-Threonine Kinases Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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