Attenuated AMPA Receptor Expression Allows Glioblastoma Cell Survival in Glutamate-Rich Environment 英文参考文献.docVIP

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Attenuated AMPA Receptor Expression Allows Glioblastoma Cell Survival in Glutamate-Rich Environment 英文参考文献.doc

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Attenuated AMPA Receptor Expression Allows Glioblastoma Cell Survival in Glutamate-Rich Environment 英文参考文献

AttenuatedAMPAReceptorExpressionAllows GlioblastomaCellSurvivalinGlutamate-Rich Environment DannisG.vanVuurden1,2.,MaryamYazdani1.,IngeborgBosma3,AartJ.F.Broekhuizen1,TjeerdJ. Postma3,JanJ.Heimans3,PaulvanderValk4,EleonoraAronica5,BakhosA.Tannous6,7 ,Thomas Wu¨rdinger2,6,8,GertjanJ.L.Kaspers1,JacquelineCloos1,2* 1Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, the Netherlands, 2Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, Amsterdam, the Netherlands, 3Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands, 4Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands, 5Department of Pathology, AMC University Hospital, Amsterdam, the Netherlands, 6Molecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America, 7Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America, 8DepartmentofNeurosurgery,VUUniversityMedicalCenter,Amsterdam,theNetherlands Abstract Background: Glioblastoma multiforme (GBM) cells secrete large amounts of glutamate that can trigger AMPA-type glutamatereceptors(AMPARs).ThiscommonlyresultsinNa andCa -permeabilityandtherebyinexcitotoxiccelldeathof thesurroundingneurons.HereweinvestigatedhowtheGBMcellsthemselvessurviveinaglutamate-richenvironment. + 2+ MethodsandFindings:Insilicoanalysisofpublishedreportsshowsdown-regulationofallionotropicglutamatereceptors inGBMascomparedtonormalbrain.Invitro,inallGBMsamplestested,mRNAexpressionofAMPARsubunitGluR1,2and4 wasrelativelylowcomparedtoadultandfetaltotalbrainmRNAandadultcerebellummRNA.Thesefindingswereinline withprimaryGBMsamples,inwhichproteinexpressionpatternsweredown-regulatedascomparedtothenormaltissue. Furthermore, mislocalized expression of these receptors was found. Sequence analysis of GluR2 RNA in p