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研究生:李欣倫
研究生(外文):Hsin Lun Li
論文名稱:Nanog對人類鼻咽癌細胞分化之影響
論文名稱(外文):Effect of Nanog expression on the differentiation of human NPC cell line
指導教授:陳君侃陳君侃引用關係
指導教授(外文):J. K. Chen
學位類別:碩士
校院名稱:長庚大學
系所名稱:基礎醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
論文頁數:57
中文關鍵詞:蛋白質激酶C鼻咽癌細胞分化
外文關鍵詞:Nanogprotein kinase CPKCnasopharyngeal carcinomadifferentiation
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西元2003年 Chambers 及 Mitsui 等人研究發現,在胚胎發育初期 Nanog 會大量地表現,其表現具有調控胚胎幹細胞的多功能性(pluripotency)及抑制其分化的作用。而近來研究發現除了胚胎幹細胞之外,胚胎癌細胞及胚胎生殖細胞中 Nanog 也會大量表現。反之在有一定分化程度的細胞Nanog 是沒有表現的。由此似乎可以確定 Nanog 有著抑制細胞分化的作用。又因 Nanog 也在癌細胞中的發現,更指出了 Nanog 在癌化過程中可能扮演一個重要的角色,尤其是在調控癌細胞分化的功能上。

而多年來的研究已確立 PKC(protein kinase C)在癌細胞分化上也扮演重要的調控角色。過去文獻也指出:在某些癌細胞的癌化過程中,會出現一些只在胚胎幹細胞中才有表現的基因,例如:Nanog。可見癌細胞與幹細胞在基因的表現上,有一些類似之處,而基於對癌細胞分化的影響上,PKC 與 Nanog 皆是扮演重要的調控角色,因此我們即想進一步探討在癌細胞的分化上,PKC 與 Nanog 兩者之間的關聯性。又鼻咽癌好發率以亞洲人最高,所以深入了解鼻咽癌的生理現象是必須的,因此本研究將以鼻咽癌細胞作為觀察 model,探討 PKC 與 Nanog 兩者之間的關係,並觀察 PKC 與 Nanog 對於鼻咽癌細胞分化的影響。

由實驗結果發現在鼻咽癌細胞株或是鼻咽部正常細胞株,當PKC 的活性受到抑制時,Nanog 的表現會增加,即PKC 的活性與 Nanog 的表現皆呈現負相關;而在癌細胞分化上的觀察,在第三天和第七天皆發現,Involucrin 會因PKC受到抑制而降低表現,癌細胞的分化程度則是與 PKC 的活性呈現正相關,同時 Nanog 會因 PKC 受到抑制而表現增加,實驗結果似乎顯示 Nanog 的表現與分化程度的變化有著關聯性,所以我們再進一步的確認 PKC、Nanog和癌細胞分化三者之間的關係為何,發現在鼻咽癌細胞中,PKC 的確會透過 Nanog 去影響細胞分化。
In 2003, Chambers and Mitsui have found that Nanog is expressed specifically in undifferentiated embryonic stem (ES) cells and have shown that it is essential for the maintenance of pluripotency in ES cells. Nanog is highly expressed in ES cells and embryonic carcinoma (EC) cells, but it is usually not expressed in adult tissues, suggesting Nanog is crucial in preventing cell differentiation. Recently, Nanog has also been found to be expressed in some tumours. Piestun D et al. (2006) showed that Nanog can be oncogenic and transforms fibroblasts. It suggests that Nanog may be related to cancer cell proliferation and differentiation.

The role of PKC in carcinogenesis has been recognized for decades. PKC isoforms are often overexpressed in disease states such as cancer. Mutations in cancer related genes eventually lead to the development of cancer. Vast majority of the studies have demonstrated that PKC activity is associated with differentiation of cancer cells. In this paper we showed that Nanog can be induced by PKC inhibitors in human nasopharyngeal carcinoma cell line, NPC076, suggesting that Nanog may be involved in PKC induced differentiation of NPC cell lines.
目 錄

指導教授推薦書…………………………………………………………
口試委員會審定書………………………………………………………
授權書………………………………………………………………….iii
誌謝……………………………………………………………………. iv
中文摘要………………………………………………………………..v
英文摘要……………………………………………………………….vii
目錄 …………………………………………………………………..viii
第一章 前言……………………………………………………………1
第二章 研究目的………………………………………………………10
第三章 實驗方法與材料………………………………………………11
第四章 結果……………………………………………………………19
第五章 討論……………………………………………………………24
參考文獻 ………………………………………………………………38
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