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研究生:彭大倫
研究生(外文):Ta Lun Peng
論文名稱:食道癌的上皮間質型態轉化相關轉移性型態之基因轉譯圖像研究
論文名稱(外文):Transcriptome profiling of invasion phenotype associated with epithelial-mesenchymal transition in esophageal cancer
指導教授:鄭恩加
指導教授(外文):A. J. Cheng
學位類別:碩士
校院名稱:長庚大學
系所名稱:醫學生物技術研究所
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
論文頁數:76
中文關鍵詞:食道癌轉移上皮間質型態轉化
外文關鍵詞:ESCmetastasisEMT
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在台灣,食道癌是致死率前十名的癌症,已知食道癌具有相當高的轉移潛力,可能因此造成較差的預後,目前影響其轉移的分子機制並不清楚,因此在本研究專題將著重在發現與食道癌轉移相關的基因,我們重複使用Matrigel循序篩檢的方法,成功的從食道癌細胞株 (CE48) 中建立出高侵犯性的子代細胞株,也證明了子代細胞株的確擁有較高的侵犯以及爬行能力;另一方面我也發現這些子代細胞型態會隨著代數增加而有所改變,從趨於圓形的上皮細胞型態轉成較細長的間質細胞型態,當進一步檢測EMT的標誌蛋白表現,則更進一步確認Matrigel的篩選促進EMT的發生。爾後我們以cDNA microarray分析親代與子代細胞間的基因表現差異,找到一些符合細胞功能變化的基因與訊號路徑,我們也確認了包含TKT、MYH9、Filaming A、Gp96等基因在侵犯性子代會過量表現,推測這些基因可能與EMT及轉移有正向的關係,更進一步找到以siRNA去抑制TKT的表現,發現此舉將讓細胞的侵犯與爬行能力下降,也影響ERK/MAPK的訊息傳遞,固TKT將可能透過調控ERK/MAPK路徑來影響EMT,而造成食道癌細胞的轉移。
The esophageal cancer (ESC) is one of the ten-leading cancers in Taiwan with highly metastatic potential. The aim of this study was to identify relevant alterations of gene expression associated with the invasive phenotype of ESC. To reduce heterogeneity and to obtain data on genes specifically involved in invasive mechanisms, we have established a highly invasive ESC subline (CE48t/VGH) through 10 passages of in vitro Matrigel selections. This subline exhibited increases of invasion and migration abilities with the ascending generations, in accompany of morphological alteration from epithelial type to mesenchymal type, indicating an epithelial- mesenchymal transition (EMT) occurred during this Matrigel selection. In support of this finding, five molecular EMT markers were also examined accordingly. Affymetrix cDNA microarray was used to compare the transcriptomes between the parental and the EMT-associated invasion subline. Heretical cluster and algorithmic analyses of the microarray dataset revealed that several functional pathways associated with these phenotypic alterations. Among these 10 genes were examined for the potential differential expressions between parental and subline by RT-PCR or western blot analysis. In which, TKT, MYH9, Filaming A, Fibronectin, Gp96, Slug and IAGAP1 were found over-expressed in the invasion subline, suggesting a positive association in the regulation of EMT-associated invasion. Knockdown of TKT by siRNA further demonstrated suppression of cell invasion in the ESC cells. In conclusion, results of this study provide molecular knowledge in the EMT-associated metastasis in ESC
論文指導教授推薦書..………………………………………….………..i
論文口試委員審定書………………………………………..………..…ii
長庚大學博碩士紙本論文著作授權書……………………………...…iii
致謝……………..…………………………………………….…………iv
中文摘要…………………………………………………………………vi
Abstract………………………………………………………………….vii
Background………………………………………………………….…....1
Epideminology of esophageal cancer (ESC)………………….……..………...1
Poor prognosis and high invasion / metastasis of ESC………….……….……3
Genes related to ESC invasion / metastasis have not been well defined……...6
Potential invasive associated genes in ESC……………………………..…….7
Study aim and approach……………………………………………..…..11
Materials and Methods……………………………………………….....13
Results…………………………………………………………………..20
Discussion………………………………………………………………27
References………………………………………………………………32
Table and Figure…………………………………………………….…..40
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