JDP2在TGF-β1诱导的人胰腺癌细胞系Panc-1上皮向间质转化中的作用  

JDP2 suppresses transforming growth factor-β1-induced epithelial-mesenchymal transition in human pancreatic cancer cell line Panc-1

作　　者：许元鸿[1] 刘哲[1] 郭克建[1] 杜瑞霞[2] 王春雁[3] 

机构地区：[1]中国医科大学附属第一医院胰腺外科,辽宁省沈阳市110001 [2]沈阳医学院附属奉天医院耳鼻咽喉科,辽宁省沈阳市110024 [3]中国医科大学医学影像系,辽宁省沈阳市110001

出　　处：《世界华人消化杂志》2011年第28期2931-2936,共6页World Chinese Journal of Digestology

摘　　要：目的:研究JDP2与TGF-β1诱导的人胰腺癌细胞系Panc-1上皮向间质转化之间的关系.方法:实验分为空白对照组、JDP2转染组、空质粒转染组3组,并分别用P、P-J-T、P-V-T缩写代表.用pCEFL-HA-JDP2质粒和pCEFL空质粒瞬时转染人胰腺癌细胞系Panc-1,48h之后应用TGF-β1分别刺激JDP2转染和空质粒转染组细胞48h.以正常的Panc-1细胞为空白对照组,仅加等量的PSB.倒置显微镜下观察各组细胞的形态学变化的差异;应用RT-PCR及Westernblot的方法检测E-cadherin及vimentin的蛋白及mRNA表达变化;应用Transwell侵袭实验观察各组细胞的迁移能力.结果:P-J-T组能够明显抑制由TGF-β1诱导产生的EMT.与P组相比,P-J-T组大部分细胞没有明确的形态学上的变化,E-cadherin及vimentin蛋白及mRNA表达变化不明显,迁移能力亦无明确差异(48.0±5.3vs52.0±7.2),未成功诱导EMT;而P-V-T组Panc-1细胞大多数变成长梭形,细胞间紧密连接丢失,E-cadherin表达明显降低(mRNA表达:P<0.01;蛋白表达:P<0.05),vimentin蛋白及mRNA表达明显升高(P<0.01),侵袭至小室下室的细胞明显增加(48.0±5.3vs81.0±10.7,P<0.01),出现非常显著的上皮向间质转化特征.结论:JDP2具有明显抑制EMT的作用,JDP2转染后的胰腺癌细胞系可以明显抑制由TGF-β1诱导的EMT,这使得JDP2有可能成为新的胰腺癌的靶向治疗因子.AIM：To determine the correlation between overexpression of Jun dimerization protein 2（JDP2） and epithelial-mesenchymal transition（EMT） in human pancreatic cancer cell line Panc-1.METHODS：Panc-1 cells were divided into three groups：negative control group,JDP2-transfected group,and empty vector-transfected group.The JDP2-transfected group and empty vector-trans-fected group were transiently transfected withPCEFL-HA-JDP2 vector and pCEFL vector,respectively.Untreated Panc-1 cells were used asnormal controls.Forty-eight hours after transfection,cells were treated with TGF-β1（10 ng/mL）.Cell morphological alternations were examinedby phase-contrast microscopy.The expressionof mesenchymal marker vimentin and epithelialmarker E-cadherin was detected by RT-PCR andWestern blot.Cell migration was determined byTranswell motility assay.RESULTS：TGF-β1-induced EMT was inhibited inthe JDP2-transfected group.Compare to the negative control group,cells in the JDP2-transfectedgroup showed no fibroblastic morphology andno signif icant changes in the levels of E-cadherinand vimentin and in migration ability（48.0 ± 5.3 vs52.0 ± 7.2）.However,cells in the vector-transfectedgroup showed loss of cell-cell contacts,f ibroblasticmorphology,decreased expression of E-cadherin（mRNA：P 0.01;protein：P 0.05）,increasedexpression of vimentin（P 0.01） and migrationability（48.0 ± 5.3 vs 81.0 ± 10.7,P 0.01） whencompared to the negative control group.CONCLUSION：JDP2 can inhibit TGF-β1induced EMT in Panc-1 cells and may be a molecular target for pancreatic carcinoma therapy.

关 键 词：Jun二聚化蛋白2 胰腺癌 上皮向间质转化 转化生长因子-Β1 

分 类 号：R735.9[医药卫生—肿瘤]