Significance of Heterogeneous Twist2 Expression in Human Breast Cancers 英文参考文献.docVIP

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Significance of Heterogeneous Twist2 Expression in Human Breast Cancers 英文参考文献.doc

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Significance of Heterogeneous Twist2 Expression in Human Breast Cancers 英文参考文献

SignificanceofHeterogeneousTwist2Expressionin HumanBreastCancers YubinMao1*,NiniZhang1,JinfeiXu1,ZhijieDing2,RongrongZong3,ZuguoLiu3* 1DepartmentofPathophysiologyinBasicScience,MedicalCollegeofXiamenUniversity,Xiamen,Fujian,China,2DepartmentofSurgery,ZhongshanHospitalofXiamen University,Xiamen,Fujian,China,3EyeInstituteandXiamenEyeCenter,MedicalCollegeofXiamenUniversity,Xiamen,Fujian,China Abstract Background:Twist2(Dermo1)hasbeenshowntomediatetheepithelial-mesenchymaltransition(EMT)topromotetumor invasionandevenmetastasis.However,theinvolvementofEMTinbreastcancerprogressionishighlydebated,partially due to clinical observations showing that the majority of human breast carcinoma metastases express E-cadherin and maintaintheirepithelialmorphology.ThemolecularmechanismbywhichTwist2participatesinEMTofbreastcancerinvivo remainspoorlyunderstood. Methods:WeexaminedTwist2expressionpatterninhumanbreastcarcinomasbywesternblotandtissuemicroarray,and analyzedTwist2cellularlocalizationbyconfocalmicroscopy,cellfractionationandotherapproaches. Results:Twist2expressionwassignificantlyincreasedinbreastcancer.CytoplasmicTwist2positivecancercellsexpressing E-cadherinonthecellularmembraneweremainlylocatedattumorcenterofprimarycarcinomasandlymphmetastases, whilecancercellswithnuclearTwist2clearlyshowedlossofE-cadherinandweredetectedattheinvasivefrontinductal breastcarcinomas.Inaddition,ectopicallystable-expressedTwist2wasfoundtolocalizeinthecytoplasmofcancercells. Collectively, these data indicate that upregulation of cytoplasmic Twist2 is correlated with tumor histological type and tumormetastasisinhumanbreastcancers. Conclusion: The differential cellular distribution of Twist2 may be associated with tumor progression. The cytoplasmic Twist2 in cancer cells at tumor center of primary carcinomas and lymph metastases contributes to the maintenance of epithelialcancercharacteristicsexpressingE-cadherininanoninvasivestate,whilethenuclearTwist2atthecancerinvasion frontactivatesEMTtodepri