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研究生:游舒婷
研究生(外文):Shu-Ting Yu
論文名稱:TSC2抑制腸癌細胞的生長與p53有關
論文名稱(外文):Inhibition of colon cancer cell growth mediated by TSC2
指導教授:陳一村
指導教授(外文):I-Tsuen Chen
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:醫學生物技術暨檢驗學系暨研究所
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
語文別:中文
論文頁數:65
中文關鍵詞:結節性硬化症缺陷瘤
外文關鍵詞:TSC22DGmTORTSC1IR
相關次數:
  • 被引用被引用:2
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  • 下載下載:56
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蛋白質合成會受到多重的細胞環境所調控,包含細胞能量的多寡。營養物質、能量或是AKT這些訊息都可以活化 mTOR, mTORㄧ種對細胞生長、存活的中心調控者。 其活化部分歸功於 S6K蛋白的活化進而影響到蛋白質合成。 mTOR 的活性受到TSC1/TSC2 複合物的負面調節,主要是 TSC2蛋白 ,它會調節細胞能量反應。 TSC2 是受 p53所調控的基因並且會受到 PI3K-AKT 路徑的負面調節。 2DG 是ㄧ種葡萄糖的類似物,會誘發葡萄糖匱乏而引起細胞氧化代謝壓力而毒殺人類癌症細胞。
我們的實驗結果顯示,在 RKO 細胞裡, 野生型 p53 與 TSC2 都會受到 IR 與 2DG 的處理而活化。但是在 HT29 (含p53 mutant) 與含有 mutant p53 RKO 卻不明顯。只有在 RKO 細胞才會發生 TSC2 的活化與降低 S6K 的表現量,所以我們認為使用 IR 與 2DG 的處理,進而抑制細胞生長是要依賴 p53 。我們的實驗結果也顯示,癌症細胞若為 p53 野生型,經由 IR 或是2DG 的處理會活化 TSC2 並且抑制 mTOR 路徑,進而抑制癌症細胞生長或是增強毒殺力。
Protein synthesis is regulated by multiple cellular conditions including cellular energy levels. Signals from intercellular nutrients, energy and from AKT activate mTOR (mammalian target of rapamycin), a central regulator for cell growth and proliferation. This is achieve in part by driving protein synthesis through activating ribosomal protein S6 kinase 1(pS6K). mTOR activity is negatively regulated by TSC1/TSC2 complex, mainly TSC2 (tuberin) protein, which mediates cellular energy response. TSC2 is
a p53-regulated gene and is negatively regulated by PI3K-AKT pathway. The glucose analogue 2DG induces glucose deprivation which has been shown to cause cytotoxicity by inducing metabolic oxidative stress in human cancer cells. 2DG also induces TSC2 phosphorylation which inhibits mTOR signaling.
Our data shows that both p53 and TSC2 were activated in IR or 2DG treated RKO cells but were not apparent in HT29 cells (contain mutant p53) or isogenic RKO mt p53.
The activated TSC2 correlated with decreased ribosomal
pS6K protein expression only in RKO cells ,suggesting inhibition of cell growth by IR or 2DG is p53 dependent. Our data suggest that for tumor cells containing wt p53,
IR or/and metabolic stress by 2DG could activate TSC2 and inhibit mTOR pathway, thus inhibit tumor cell growth or enhance cytotoxicity.
[目 錄]
頁數
中文摘要 2
英文摘要 3
第一章 緒論 4∼9
第二章 材料與方法 10∼25
第三章 結果 26∼31
第四章 討論 32∼34
第五章 參考文獻 35∼42
第六章 圖表 43∼55
第七章 Supplemental data 56∼58
附錄 59∼65
第五章 參考文獻
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