S100A14在食管鱗癌中的遺傳變異及其功能研究.pdf

1、北京協(xié)和醫(yī)學(xué)院中國醫(yī)學(xué)科學(xué)院博士學(xué)位論文S100A14在食管鱗癌中的遺傳變異及其功能研究姓名：陳洪巖申請學(xué)位級別：博士專業(yè)：細(xì)胞生物學(xué)指導(dǎo)教師：劉芝華20090101北京協(xié)和醫(yī)學(xué)院博：=學(xué)位論文AbstractSl00proteinsplayimportantrolesintumorigenesisandmetastasisOurpreviousstudybysemiquantitativeRTPCRshowedthattheexpre

2、ssionlevelofsixteenmembersofS100familyincludingS100A14wassignificantlyalteredinEsophagealSquamousCellcarcinoma(ESCC)InordertofurthercharacterizeexpressionpatternofS100A14andtherelationshipwithclinicopathologicalfeatures，

3、WesternblotandimmunohistochemicalanalysiswereperformedinprimarytumorsandmatchednormaltissuesandtissuemicroarrayrespectivelyTheresultsindicatedthattheexpressionofS100A14wasdownregulatedinESCCsamplescomparedwithmatchednorm

4、alcounterpartsStatisticalanalysisrevealedthattherewassignificantcorrelationbetweenS100A14expressionanddifferentiationgradeinESCCFunctionalstudiesindicatedthatS100A14overexpressionpromotedcelladhesiontoFibronectincoatedwe

5、llsandinvasivecapabilities，butinhibitedcellmotilitycapabilityInaccordancewithaboveresults，S100AI4RNAipromotedKYSE150cellmotilitycapabilityMolecularmechanismstudiesshowedthatEcadherinwasup—regulatedwhereasNcadherinwasdown

6、regulatedinS100A14RNAicellsHowevertheprecisemechanismstillneedsfurtherinvestigationInthesecondpart，weexaminedwhethertherearefunctionalgeneticvariantsinthe$100A14locus，andassessedtheirassociationwithsusceptibilitytoesopha

7、gealsquamouscellcarcinoma(ESCC)ThirtyindividualDNAsamplesweresequencedtosearchforgeneticvariations，andthefunctionofthevariantswasinvestigatedbyaseriesofbiochemicalassaysFoursinglenucleotidepolymorphisms，43AG，461GA，1493AG

8、and1545ATwereidentifiedinthe$100A14locus，andallwereinabsolutelinkagedisequilibriumThe461GAchangewasfoundtobeafunctionalvariantaffectingp53binding，whichmightabolishnegativefeedbackloopinthep53regulationAcase—controlanalys

9、iswasperformedin1021patientswithESCCand1253controlsubjectsOddsratios(ORs)and95％confidenceintervals(CIs)wereestimatedbylogisticregressionTheresultsshowedthatthe461AalleleisassociatedwithanincreasedsusceptibilitytoESCCcomp