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研究生:劉怡佳
研究生(外文):Yi-Jia Liu
論文名稱:RECK蛋白之Kazalmotifs對MMP-2和MMP-9活性與肺腺癌轉移的功能探討
論文名稱(外文):Study of Kazal motifs of RECK protein on MMP-2 and MMP-9 activity and metastasis of lung adenocarcinoma
指導教授:洪文俊洪文俊引用關係
指導教授(外文):Wen-Chun Hung
學位類別:碩士
校院名稱:國立中山大學
系所名稱:生物醫學研究所
學門:工程學門
學類:生醫工程學類
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:62
中文關鍵詞:肺腺癌轉移
外文關鍵詞:RECKMMP-9
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RECK (reversion-inducing cysteine-rich protein with Kazal motifs)基因可以逆轉 v-Ki-ras 所造成的小鼠 NIH3T3 細胞轉型。由於 RECK 蛋白主要功能為調控間質金屬蛋白酶活化,所以具有抑制癌細胞轉移的作用。在 RECK 蛋白結構中段具有三個 serine protease inhibitor-like domains (SPIs) (第 635~654、716~735 和 754~772 個氨基酸) 與 Kazal motif 相似;Kazal motif 是一種具有peptidase inhibitor 的功能區,富含雙硫鍵和一些 α、β 折疊。其中第一段 SPI 與 Kazal motif 一致,稱為 K1,其餘兩段與 Kazal motif 相似但不完全一致,分別稱為 K2,K3。這些 SPI-like domains 可能對於 RECK 抑制 MMP 的蛋白水解能力有調控的作用。
實驗室之前的研究指出 Kazal-like motifs 2~3 對於 RECK 抗癌細胞轉移侵犯扮演重要的角色。所以本研究進一步探討不同 Kazal motif 功能區的短片段對 MMP 活性與癌細胞轉移能力的作用,結果發現 Kazal-like motif 2 可以經由抑制 MMP-9 的分泌與活性而導致癌細胞的侵犯與轉移能力下降。我們推論 Kazal-like motif 2 對於 RECK 抗癌細胞轉移侵犯所扮演的角色是非常重要的。
RECK stands for ‘reversion-inducing cysteine-rich protein with Kazal motifs’. This gene was initially discovered by screening a human fibroblast cDNA library for genes giving rise to reversion-inducing clones when transfected into v-Ki-ras transformed NIH3T3 cells. The key action of RECK is to inhibit matrix metalloproteinases (MMPs), and it has a significant effect on limiting tumor invasion. Located within the middle part of RECK protein are three serine protease inhibitor-like (SPI) domains (635-654,716-735 and 754-772 amino acids, respectively) which are similar to Kazal motif. Kazal motif is a peptidase inhibitor motif containing disulfide bonds with small alpha and beta folds. The first of these SPI is identical to the Kazal motif (named as K1) and the other two SPIs are highly similar to the Kazal motif (named as K2 & K3). Given RECK is a MMP inhibitor, these SPI-like domains are likely to have a significant role in MMP inhibition.
Our previous data indicated that K23 motifs of RECK protein can inhibit MMP-9 secretion and activity and attenuate metastasis of lung cancer cells. To go a step further, we constructed secretory mammalian expression vectors which could produce K1, K2 and K3 to investigate their effect on MMP activity and cell invasion. We found that K2 also exhibited inhibitory activity on MMP activity and cell invasion. Thus, these finding indicate that the K2 domain of RECK function may be developed as a peptide inhibitor of tumor invasion.
中文摘要 2
英文摘要 3
縮寫語 4
前言 5
研究方向 9
實驗材料與方法 10
實驗結果 30
討論 34
圖表及說明 38
參考文獻 51
附圖 54
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