臺灣博碩士論文加值系統

在合成O-glycan 結構的過程中，Galβ1,3GalNAc稱為T antigen 或Core 1 structure，是一個根部的醣類結構，此結構在正常的表皮組織中會被其他糖類轉換酵素延伸為更長的醣類結構；而在許多的癌症中卻表現著大量的T antigen結構，而此結構被證明可以增加癌細胞轉移到肝臟的機率。C1GalT1是core 1 synthase會將UDP-Gal接到GalNAc-Ser/Thr的結構上形成T antigen；而C1GALT1-specific chaperone 1 (COSMC)是C1GalT1的專一性chaperone，使C1GalT1具有酵素活性所必須。T antigen結構在腫瘤中大量表現的機制目前還不清楚。我們推測COSMC可以調控大腸直腸癌細胞T antigen的表現並進而影響癌細胞的行為。在我的研究中發現，COSMC基因過量表現的百分比在較惡性Dukes’ C、D族群的病人中是增加的。當我們將COSMC基因轉染HCT116，可以發現細胞表面T antigen的表現量是顯著上升。更進一步的研究中發現，過量表現COSMC的癌細胞HCT116會促進其增生 (proliferation)、爬行 (migration)、入侵 (invasion)的能力，增強形成colony的能力。在免疫缺陷鼠(SCID mice)的腫瘤生成模式中，過量表現COSMC會促進腫瘤變大。這些發現表示COSMC可能在促進大腸直腸細胞癌化的過程中扮演著重要的角色。未來，在治療大腸直腸癌方面，COSMC亦有成為標靶藥物治療的潛力。

口試委員會審定書…………………………………………i
誌謝…………………………………………………………ii
中文摘要……………………………………………………iii
英文摘要……………………………………………………iv
總目錄………………………………………………………v
圖目錄………………………………………………………vi
縮寫表………………………………………………………vii
前言…………………………………………………………1
實驗材料與方法……………………………………………5
結果…………………………………………………………16
討論…………………………………………………………23
參考文獻……………………………………………………27

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