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系統識別號 U0007-2107201107481000
論文名稱(中文) β-catenin控制第一型黏蛋白於乳癌細胞核運輸之探討
論文名稱(英文) β-catenin-mediated nuclear localization of cytoplasmic domain of MUC1 in breast cancer
校院名稱 臺北醫學大學
系所名稱(中) 臨床醫學研究所
系所名稱(英) Graduate Institute of Clinical Medicine
學年度 99
學期 2
出版年 100
研究生(中文) 蘇厚有
研究生(英文) Hou-Yu Su
學號 M118098004
學位類別 碩士
語文別 中文
口試日期 2011-06-27
論文頁數 58頁
口試委員 委員-黃蕙君
共同指導教授-陳永興
委員-劉俊仁
委員-林豐彥
指導教授-張育嘉
中文關鍵字 乳癌  黏蛋白  核運輸 
英文關鍵字 breast cancer  MUC1  mucin  catenin 
學科別分類
中文摘要 乳癌為台灣女性十大惡性腫瘤發生率的第一位,近年研究報告顯示乳癌細胞第一型黏蛋白(MUC1)過度表現且其中MUC1-CD(cytoplasmic domain of MUC1)影響細胞的基因調控,促使癌細胞生長;另一方面,β-catenin為細胞骨架的構成要素,亦是乳癌重要的致癌蛋白,透過WNT/β-catenin訊息傳遞路徑到達細胞核內影響基因調控,同時發現MUC1-CD上具有β-catenin的結合位置,故我們推測MUC1-CD可能與β-catenin於腫瘤調控中具有著某種程度的關聯。首先以免疫共沉澱法(co-immunoprecipitation)分析β-catenin及MUC1-CD的關係,發現MCF7細胞中β-catenin能結合於MUC1-CD;進一步分別利用RNAi的技術及基因大量表現的方法,抑制或增強β-catenin的表現量,並以分離細胞質與細胞核蛋白質方式,觀察MUC1-CD於細胞中分布情形及在核中的表現量變化。主要是透過了解β-catenin的表現量是否能夠影響MUC1-CD進入細胞核的比例,結果發現:於MCF7細胞中降低β-catenin的表現量後,MUC1-CD於細胞核的量亦明顯地降低;而在MDA-MB231細胞中增加β-catenin的表現量後,MUC1-CD於細胞核的量亦明顯地增加,另一方面於MCF7細胞及MDA-MB231細胞中MUC1的mRNA及MUC1-CD細胞總蛋白質的表現量無明顯改變,這個結果顯示改變β-catenin的表現量會影響MUC1-CD細胞質及細胞核的分布。由實驗的結果可以得到以下結論:乳癌細胞透過β-catenin和MUC1-CD蛋白質的交互作用控制MUC1-CD進入細胞核的比例,所以β-catenin控制MUC1-CD的細胞核運輸
英文摘要 In Taiwan, breast cancer has been the most common malignancy in women. Recently, it is reported that the mucin 1 (MUC1) has been over-expressive on the cell membrane of breast cancer cells. The cytoplasmic domain of mucin 1 (MUC1-CD) can influence gene regulation in breast cancer. In the other hand, β-catenin is one component of the cytoskeleton. It is also an oncoprotein in relationship with WNT/β-catenin signaling pathway and influences gene regulation in breast cancer. There is a docking site on MUC1-CD for β-catenin. So, the interaction between MUC1-CD and β-catenin may influence oncogenesis in breast cancer. First, we researched the reciprocal interaction between β-catenin and MUC1-CD by co-immunoprecipitation. β-catenin can be associated with MUC1-CD intracellularly. Further, we used the techniques of RNA interference and gene over-expression to manipulate the expression of β-catenin. Additionally, we observed the changes of cytoplasmic and nuclear MUC1-CD in MCF7 and MDA-MB231 cells by compartment protein extraction. We wanted to demonstrate nuclear localization of MUC1-CD by augmenting or lowering the expression of β-catenin. It was resulted that the quantity of the nuclear MUC1-CD decreased after the expression of β-catenin was lowered in MCF7 cells. In contrast, the amount of the nuclear MUC1-CD increased after β-catenin was over-expressive in MDA-MB231 cells. In the other hand, mRNA of MUC1 and total protein of MUC1-CD were unaltered significantly in both of MCF7 and MDA-MB231 cells. Therefore, the up and down-expression of β-catenin was correlative with the quantity of MUC1-CD in the cell nucleus.It is concluded that β-catenin can control the nuclear localization of MUC1-CD by reciprocal interaction in breast cancer.
論文目次 標題.............................................. i
審定書............................................ ii
授權書 .......................................... iii
保密同意書........................................ iv
致謝.............................................. v
縮寫表 ......................................... vi
目錄............................................. vii
中文摘要........................................... 1
英文摘要........................................... 2
第一章 緒論........................................ 3
第二章 實驗材料與方法……………………………………… 10
第三章 結果………………………………………………… 15
第四章 討論…………………………………………………… 20
第五章 結論…………………………………………………… 24
參考資料…………………………………………………………27
圖表………………………………………………………………31
附錄………………………………………………………………46
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