Ezrin对转移性乳腺癌上皮间质转化的调控研究

发布时间：2018-05-15 13:33

本文选题：乳腺癌 + 转移　；参考：《南京医科大学》2015年硕士论文

【摘要】：上皮-间质转化(epithelial-mesenchymal transition,EMT),是指上皮细胞通过特定程序转化为间质表型细胞的生物学过程,在生理和病理过程中发挥重要作用,近年发现其与乳腺癌转移密切相关。本研究团队前期建立的人源性乳腺微环境小鼠乳腺癌模型中,发现原代细胞与亲代细胞相比,细胞形态发生梭形改变,迁移侵袭能力增强,EMT标志物发生改变,提示原代细胞发生EMT改变,新的EMT通路及蛋白有望被发现。进一步通过蛋白质组分析在两种细胞中得到81种差异蛋白,其中埃兹蛋白(ezrin)和皮动蛋白(cortactin)发生显著的改变。本实验通过慢病毒转染MDA-MB-231和SUM-1315细胞系,成功下调细胞中ezrin的表达。Ezrin下调后,细胞迁移和侵袭能力降低,EMT标志物钙黏蛋白E(E-cadherin)表达增高,α-平滑肌动蛋白(α-SMA)表达降低,转录因子snail,slug,twist1,twist2部分发生下调改变,MDA-MB-231细胞形态由间质转变为上皮表型。伴随ezrin下调,cortactin表达降低,而cortactin并不能引起ezrin的改变,免疫共沉淀表明两种蛋白之间存在直接联系,乳腺癌组织芯片免疫组化研究发现ezrin高表达与cortactin高表达密切相关。目前研究发现ezrin通过自身磷酸化上调cortactin表达促进乳腺癌发生EMT,ezrin和cortactin作为EMT通路中的关键蛋白,可能成为未来治疗乳腺癌的潜在靶点。
[Abstract]:Epithelial-mesenchymal transition (EMT) is a biological process in which epithelial cells are transformed into stromal phenotypic cells through a specific procedure and play an important role in physiological and pathological processes. It has been found that EMTT is closely related to breast cancer metastasis in recent years. In the mouse breast cancer model of human breast microenvironment established by our team, we found that the primary cells had spindle shape change and enhanced migration and invasion ability, and the EMT markers were changed compared with the parental cells. These results suggest that EMT changes occur in primary cells, and new EMT pathways and proteins are expected to be discovered. Further, 81 differentially expressed proteins were obtained by proteome analysis, including Ezrinin and cortactin. In this study, MDA-MB-231 and SUM-1315 cells were transfected with lentivirus. After down-regulation of ezrin expression. Ezrin down-regulated, the expression of E-cadherin, a marker of E-cadherin, was increased, and the expression of 伪 -smooth muscle actin (伪 -SMAs) was decreased. The down-regulation of transcription factor snailslug1 / twist2 changed the morphology of MDA-MB-231 cells from interstitial to epithelial phenotypes. Ezrin down-regulated the expression of cortactin, but cortactin could not induce the change of ezrin. The immunoprecipitation showed that there was a direct relationship between the two proteins. The high expression of ezrin was closely related to the high expression of cortactin in breast cancer tissue microarray immunohistochemical study. At present, it has been found that ezrin upregulated the expression of cortactin through its own phosphorylation and promoted the development of breast cancer by EMT-ezrin and cortactin as key proteins in the EMT pathway, which may become a potential target for the treatment of breast cancer in the future.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R737.9

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