| Inhibition of transient receptor potential canonical channels impairs cytokinesis in human malignant gliomas. | |
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MedLine Citation:
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PMID: 18211288 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: Glial-derived primary brain tumours, gliomas, are among the fastest growing malignancies and present a huge clinical challenge. Research suggests an important, yet poorly understood, role of ion channels in growth control of normal and malignant cells. In this study, we sought to functionally characterize Transient Receptor Potential Canoncial (TRPC) channels in glioma cell proliferation. TRPC channels form non-selective cation channels that have been suggested to represent a Ca(2+) influx pathway impacting cellular growth. MATERIALS AND METHODS: Employing a combination of molecular, biochemical and biophysical techniques, we characterized TRPC channels in glioma cells. RESULTS: We showed consistent expression of four channel family members (TRPC-1, -3, -5, -6) in glioma cell lines and acute patient-derived tissues. These channels gave rise to small, non-voltage-dependent cation currents that were blocked by the TRPC inhibitors GdCl(3), 2-APB, or SKF96365. Importantly, TRPC channels contributed to the resting conductance of glioma cells and their acute pharmacological inhibition caused an approximately 10 mV hyperpolarization of the cells' resting potential. Additionally, chronic application of the TRPC inhibitor SKF96365 caused near complete growth arrest. A detailed analysis, by fluorescence-activated cell sorting and time-lapse microscopy, showed that growth inhibition occurred at the G(2)+ M phase of the cell cycle with cytokinesis defects. Cells underwent incomplete cell divisions and became multinucleate, enlarged cells. CONCLUSIONS: Nuclear atypia and enlarged cells are histopathological hallmarks for glioblastoma multiforme, the highest grade glioma, suggesting that a defect in TRPC channel function may contribute to cellular abnormalities in these tumours. |
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Authors:
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V C Bomben; H W Sontheimer |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Cell proliferation Volume: 41 ISSN: 1365-2184 ISO Abbreviation: Cell Prolif. Publication Date: 2008 Feb |
Date Detail:
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Created Date: 2008-01-23 Completed Date: 2008-03-31 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 9105195 Medline TA: Cell Prolif Country: England |
Other Details:
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Languages: eng Pagination: 98-121 Citation Subset: IM |
Affiliation:
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Department of Neurobiology, Center for Glial Biology in Medicine, University of Alabama at Birmingham, AL 35294, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Biopsy Blotting, Western Boron Compounds / pharmacology Brain Neoplasms / metabolism, pathology* Cell Cycle* Cell Line, Tumor Cell Proliferation Glioma / metabolism, pathology* Humans Imidazoles / pharmacology Immunohistochemistry Transient Receptor Potential Channels / antagonists & inhibitors*, metabolism, physiology |
| Grant Support | |
ID/Acronym/Agency:
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R01 NS-31234/NS/NINDS NIH HHS; R01 NS-36692/NS/NINDS NIH HHS; R01 NS031234-14A1/NS/NINDS NIH HHS; R01 NS031234-15/NS/NINDS NIH HHS; R01 NS036692-08/NS/NINDS NIH HHS; R01 NS036692-09A2/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/2-aminoethoxydiphenylborane; 0/Boron Compounds; 0/Imidazoles; 0/Transient Receptor Potential Channels; 130495-35-1/1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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