Artificially Introduced Aneuploid Chromosomes Assume a Conserved Position in Colon Cancer Cells 英文参考文献.docVIP

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Artificially Introduced Aneuploid Chromosomes Assume a Conserved Position in Colon Cancer Cells 英文参考文献.doc

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Artificially Introduced Aneuploid Chromosomes Assume a Conserved Position in Colon Cancer Cells 英文参考文献

ArtificiallyIntroducedAneuploidChromosomesAssume aConservedPositioninColonCancerCells KundanSengupta1,MadhviB.Upender1,LindaBarenboim-Stapleton1,QuangTriNguyen1,StephenM.WincovitchSr.2¤,SusanH.Garfield2, MichaelJ.Difilippantonio1,ThomasRied1* 1GeneticsBranch,NationalCancerInstitute,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica,2LaboratoryofExperimental Carcinogenesis,NationalCancerInstitute,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica Background.Chromosomalaneuploidyisadefiningfeatureofcarcinomas.Forinstance,incoloncancer,anadditionalcopyof Chromosome 7 is not only observed in early pre-malignant polyps, but is faithfully maintained throughout progression to metastasis. These copy number changes show a positive correlation with average transcript levels of resident genes. An independentlineofresearchhasalsoestablishedthatspecificchromosomesoccupyawellconserved3Dpositionwithinthe interphase nucleus. Methodology/Principal Findings. We investigated whether cancer-specific aneuploid chromosomes assume a 3D-position similar to that of its endogenous homologues, which would suggest a possible correlation with transcriptional activity. Using 3D-FISH and confocal laser scanning microscopy, we show that Chromosomes 7, 18, or 19 introducedviamicrocell-mediatedchromosometransferintotheparentaldiploidcoloncancercelllineDLD-1maintaintheir conserved position in the interphase nucleus. Conclusions. Our data is therefore consistent with the model that each chromosomehasanassociatedzipcode(possiblygenedensity)thatdeterminesitsnuclearlocalization.Whetherthenuclear localizationdeterminesorisdeterminedbythetranscriptionalactivityofresidentgeneshasyettobeascertained. Citation: SenguptaK,UpenderMB,Barenboim-StapletonL,NguyenQT,WincovitchSM,etal(2007)ArtificiallyIntroducedAneuploidChromosomes AssumeaConservedPositioninColonCancerCells.PLoSONE2(2):e199.doi:10.1371/journal.pone.0000199 INTRODUCTION chromosome transfer. As in primary tumors, an incr