Molecular Predictors of 3D Morphogenesis by Breast Cancer Cell Lines in 3D Culture 英文参考文献.docVIP

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Molecular Predictors of 3D Morphogenesis by Breast Cancer Cell Lines in 3D Culture 英文参考文献.doc

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Molecular Predictors of 3D Morphogenesis by Breast Cancer Cell Lines in 3D Culture 英文参考文献

MolecularPredictorsof3DMorphogenesisbyBreast CancerCellLinesin3DCulture JuHan1,HangChang1,OrsiGiricz2,GeneeY.Lee1¤,FrederickL.Baehner3,JoeW.Gray1,MinaJ.Bissell1, ParaicA.Kenny2,BahramParvin1* 1LifeSciencesDivision,LawrenceBerkeleyNationalLaboratory,Berkeley,California,UnitedStatesofAmerica,2DepartmentofDevelopmentalandMolecularBiology, Albert Einstein College of Medicine, Bronx, New York, United States of America, 3Department of Pathology, University of California, San Francisco, San Francisco, California,UnitedStatesofAmerica Abstract Correlativeanalysisofmolecularmarkerswithphenotypicsignaturesisthesimplestmodelforhypothesisgeneration.Inthis paper, a panel of 24 breast cell lines was grown in 3D culture, their morphology was imaged through phase contrast microscopy,andcomputationalmethodsweredevelopedtosegmentandrepresenteachcolonyatmultipledimensions. Subsequently,subpopulationsfromthesemorphologicalresponseswereidentifiedthroughconsensusclusteringtoreveal three clusters of round, grape-like, and stellate phenotypes. In some cases, cell lines with particular pathobiological phenotypesclusteredtogether(e.g.,ERBB2amplifiedcelllinessharingthesamemorphometricpropertiesasthegrape-like phenotype). Next, associations with molecular features were realized through (i) differential analysis within each morphologicalcluster,and(ii)regressionanalysisacrosstheentirepanelofcelllines.Inbothcases,thedominantgenesthat arepredictiveofthemorphological signatureswereidentified.Specifically, PPARchas beenassociated withtheinvasive stellatemorphologicalphenotype,whichcorrespondstotriple-negativepathobiology.PPARchasbeenvalidatedthrough twosupportingbiologicalassays. Citation:HanJ,ChangH,GiriczO,LeeGY,BaehnerFL,etal.(2010)MolecularPredictorsof3DMorphogenesisbyBreastCancerCellLinesin3DCulture.PLoS ComputBiol6(2):e1000684.doi:10.1371/journal.pcbi.1000684 Editor:UweOhler,DukeUniversity,UnitedStatesofAmerica ReceivedJanuary27,2009;AcceptedJanuary25,2010;PublishedFebruary26,2010 Copy