N-Myc-induced up-regulation of TRPM6/TRPM7 channels promotes neuroblastoma cell proliferation
Intracellular levels of the divalent cations Ca(2+) and Mg(2+) are important regulators of cell cycle and proliferation. However, the precise mechanisms by which they are regulated in cancer remain incompletely understood. The channel kinases TRPM6 and TRPM7 are gatekeepers of human Ca(2+)/Mg(2+) me...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202149/ https://www.ncbi.nlm.nih.gov/pubmed/25277194 |
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author | Zhang, Zheng Faouzi, Malika Huang, Junhao Geerts, Dirk Yu, Haijie Fleig, Andrea Penner, Reinhold |
author_facet | Zhang, Zheng Faouzi, Malika Huang, Junhao Geerts, Dirk Yu, Haijie Fleig, Andrea Penner, Reinhold |
author_sort | Zhang, Zheng |
collection | PubMed |
description | Intracellular levels of the divalent cations Ca(2+) and Mg(2+) are important regulators of cell cycle and proliferation. However, the precise mechanisms by which they are regulated in cancer remain incompletely understood. The channel kinases TRPM6 and TRPM7 are gatekeepers of human Ca(2+)/Mg(2+) metabolism. Here, we investigated the human neuroblastoma cell line SHEP-21N in which the MYCN oncogene (encoding N-Myc) can be reversibly expressed under control of an inducible repressor. We report that N-Myc expression increases cell growth and up-regulates both TRPM6 and TRPM7 expression. Membrane current analyses reveal that endogenous TRPM6/TRPM7 currents exhibit reduced Mg·ATP suppression, increased Mg(2+) sensitivity, and diminished sensitivity to 2-APB inhibition. These properties are consistent with N-Myc-induced increase of heteromeric TRPM7/TRPM6 channels promoting Ca(2+) and Mg(2+) uptake. Genetic suppression of TRPM6/TRPM7 through siRNA inhibits cell proliferation, suggesting that N-Myc can promote neuroblastoma cell proliferation through up-regulation of divalent cation-transporting channels. |
format | Online Article Text |
id | pubmed-4202149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-42021492014-10-21 N-Myc-induced up-regulation of TRPM6/TRPM7 channels promotes neuroblastoma cell proliferation Zhang, Zheng Faouzi, Malika Huang, Junhao Geerts, Dirk Yu, Haijie Fleig, Andrea Penner, Reinhold Oncotarget Research Paper Intracellular levels of the divalent cations Ca(2+) and Mg(2+) are important regulators of cell cycle and proliferation. However, the precise mechanisms by which they are regulated in cancer remain incompletely understood. The channel kinases TRPM6 and TRPM7 are gatekeepers of human Ca(2+)/Mg(2+) metabolism. Here, we investigated the human neuroblastoma cell line SHEP-21N in which the MYCN oncogene (encoding N-Myc) can be reversibly expressed under control of an inducible repressor. We report that N-Myc expression increases cell growth and up-regulates both TRPM6 and TRPM7 expression. Membrane current analyses reveal that endogenous TRPM6/TRPM7 currents exhibit reduced Mg·ATP suppression, increased Mg(2+) sensitivity, and diminished sensitivity to 2-APB inhibition. These properties are consistent with N-Myc-induced increase of heteromeric TRPM7/TRPM6 channels promoting Ca(2+) and Mg(2+) uptake. Genetic suppression of TRPM6/TRPM7 through siRNA inhibits cell proliferation, suggesting that N-Myc can promote neuroblastoma cell proliferation through up-regulation of divalent cation-transporting channels. Impact Journals LLC 2014-07-31 /pmc/articles/PMC4202149/ /pubmed/25277194 Text en Copyright: © 2014 Zhang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Zhang, Zheng Faouzi, Malika Huang, Junhao Geerts, Dirk Yu, Haijie Fleig, Andrea Penner, Reinhold N-Myc-induced up-regulation of TRPM6/TRPM7 channels promotes neuroblastoma cell proliferation |
title | N-Myc-induced up-regulation of TRPM6/TRPM7 channels promotes neuroblastoma cell proliferation |
title_full | N-Myc-induced up-regulation of TRPM6/TRPM7 channels promotes neuroblastoma cell proliferation |
title_fullStr | N-Myc-induced up-regulation of TRPM6/TRPM7 channels promotes neuroblastoma cell proliferation |
title_full_unstemmed | N-Myc-induced up-regulation of TRPM6/TRPM7 channels promotes neuroblastoma cell proliferation |
title_short | N-Myc-induced up-regulation of TRPM6/TRPM7 channels promotes neuroblastoma cell proliferation |
title_sort | n-myc-induced up-regulation of trpm6/trpm7 channels promotes neuroblastoma cell proliferation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202149/ https://www.ncbi.nlm.nih.gov/pubmed/25277194 |
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