發(fā)布時(shí)間：2018-05-15 13:33

  本文選題：乳腺癌 + 轉(zhuǎn)移　； 參考：《南京醫(yī)科大學(xué)》2015年碩士論文

【摘要】：上皮-間質(zhì)轉(zhuǎn)化(epithelial-mesenchymal transition,EMT),是指上皮細(xì)胞通過(guò)特定程序轉(zhuǎn)化為間質(zhì)表型細(xì)胞的生物學(xué)過(guò)程,在生理和病理過(guò)程中發(fā)揮重要作用,近年發(fā)現(xiàn)其與乳腺癌轉(zhuǎn)移密切相關(guān)。本研究團(tuán)隊(duì)前期建立的人源性乳腺微環(huán)境小鼠乳腺癌模型中,發(fā)現(xiàn)原代細(xì)胞與親代細(xì)胞相比,細(xì)胞形態(tài)發(fā)生梭形改變,遷移侵襲能力增強(qiáng),EMT標(biāo)志物發(fā)生改變,提示原代細(xì)胞發(fā)生EMT改變,新的EMT通路及蛋白有望被發(fā)現(xiàn)。進(jìn)一步通過(guò)蛋白質(zhì)組分析在兩種細(xì)胞中得到81種差異蛋白,其中埃茲蛋白(ezrin)和皮動(dòng)蛋白(cortactin)發(fā)生顯著的改變。本實(shí)驗(yàn)通過(guò)慢病毒轉(zhuǎn)染MDA-MB-231和SUM-1315細(xì)胞系,成功下調(diào)細(xì)胞中ezrin的表達(dá)。Ezrin下調(diào)后,細(xì)胞遷移和侵襲能力降低,EMT標(biāo)志物鈣黏蛋白E(E-cadherin)表達(dá)增高,α-平滑肌動(dòng)蛋白(α-SMA)表達(dá)降低,轉(zhuǎn)錄因子snail,slug,twist1,twist2部分發(fā)生下調(diào)改變,MDA-MB-231細(xì)胞形態(tài)由間質(zhì)轉(zhuǎn)變?yōu)樯掀け硇�。伴隨ezrin下調(diào),cortactin表達(dá)降低,而cortactin并不能引起ezrin的改變,免疫共沉淀表明兩種蛋白之間存在直接聯(lián)系,乳腺癌組織芯片免疫組化研究發(fā)現(xiàn)ezrin高表達(dá)與cortactin高表達(dá)密切相關(guān)。目前研究發(fā)現(xiàn)ezrin通過(guò)自身磷酸化上調(diào)cortactin表達(dá)促進(jìn)乳腺癌發(fā)生EMT,ezrin和cortactin作為EMT通路中的關(guān)鍵蛋白,可能成為未來(lái)治療乳腺癌的潛在靶點(diǎn)。
[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 偽 -smooth muscle actin (偽 -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.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R737.9

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 李挺;徐美榮;黃宏偉;王鼎;朱建偉;;皮動(dòng)蛋白在結(jié)直腸腫瘤組織中的表達(dá)及臨床意義[J];中華臨床醫(yī)師雜志(電子版);2011年03期

2 Jun Wei;Zhong-Xin Zhao;Yang Li;Zhu-Qing Zhou;Tian-Geng You;;Cortactin expression confers a more malignant phenotype to gastric cancer SGC-7901 cells[J];World Journal of Gastroenterology;2014年12期

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本文編號(hào)：1892667