刘瑶;王玉东;孙笑;王晶;

• 1:上海交通大学附属国际和平妇幼保健院妇科

摘要(Abstract)：

目的:探讨RANKL对人子宫内膜癌细胞转移和上皮间质转化的影响。方法:体外构建针对细胞核因子κB受体活化因子(RANK)的过表达质粒载体(p IRES2-3FLAG-EGFP-RANK),脂质体法转染人子宫内膜癌HEC-1A细胞株,形成HEC-1ARANK细胞(过表达质粒组),并与HEC-1A^Control细胞(空白质粒组)相对照。给予1μg/ml可溶性细胞因子sRANKL处理后,细胞划痕试验检测细胞迁移能力,CCK-8试验检测细胞的增殖能力,实时荧光定量PCR(qRT-PCR)和Western blot技术分别检测EMT相关指标E-cadherin、N-cadherin及Vimentin mRNA及蛋白的表达变化。结果:经1μg/ml sRANKL刺激后,HEC-1ARANK细胞迁移能力增强(P<0.01),增殖效应没有明显改变(P>0.05),上皮性标记物E-cadherin mRNA及蛋白的表达水平下降,间质性标记物N-cadherin、Vimentin mRNA及蛋白的表达水平显著上调(P<0.01)。结论:RANKL可通过诱导HEC-1A细胞发生上皮间质转化促进子宫内膜癌的转移。

关键词(KeyWords)： 子宫内膜癌;上皮间质转化;RANKL;RANK

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金面上项目(No:81172477);; 上海市科委自然基金(No:11ZR1440800);; 上海市卫生系统优秀学科带头人培养计划(No:XBR2013097)

作者(Authors): 刘瑶;王玉东;孙笑;王晶;

DOI: 10.13283/j.cnki.xdfckjz.2015.08.009

参考文献(References)：

• [1]Siegel R,Ma J,Zou Z,et al.Cancer statistics,2014[J].CA Cancer J Clin,2014,64(1):9-29
• [2]李鹏,王志启,王建六,等.17β-雌二醇对子宫内膜癌细胞上皮间质转化诱导作用的研究[J].现代妇产科进展,2014,23(7):531-533
• [3]Battula VL,Evans KW,Hollier BG,et al.Epithelial-mesenchymal transition-derived cells exhibit multilineage differentiation potential similar to mesenchymal stem cells[J].Stem Cells,2010,28(8):1435-1445
• [4]刘瑶,王玉东.子宫内膜癌的孕激素拮抗及增敏机制[J].国际妇产科学杂志,2015,42(1):104-107
• [5]Huang Y,Zhao M,Xu H,et al.RASAL2 down-regulation in ovarian cancer promotes epithelial-mesenchymal transition and metastasis[J].Oncotarget,2014,5(16):6734-6745
• [6]Krebs MG,Metcalf RL,Carter L,et al.Molecular analysis of circulating tumor cells-biology and biomarkers[J].Nature Rev Clin Oncol,2014,11(3):129-144
• [7]Schieferdecker A,Voigt M,Riecken K,et al.Denosumab mimics the natural decoy receptor osteoprotegerin by interacting with its major binding site on RANKL[J].Oncotarget,2014,5(16):6647-6653
• [8]Wang J,Sun X,Wang Y,et al.MPA influences tumor cell proliferation,migration,and invasion induced by RANKL through PRB involving the MAPK pathway in endometrial cancer[J].Oncol Reports,2015,33(2):799-809
• [9]Boopalan T,Arumugam A,Parada J,et al.Receptor activator for nuclear factor-k B ligand signaling promotes progesterone-mediated estrogen-induced mammary carcinogenesis[J].Cancer Sci,2015,106(1):25-33
• [10]Song FN,Duan M,Liu LZ,et al.RANKL promotes migration and invasion of hepatocellular carcinoma cells via NF-k B-mediated epithelial-mesenchymal transition[J].PLo S One,2014,9(9):e108507