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Title: | 探討致癌基因MALL在非小細胞肺癌中扮演的角色 The Oncogenic Role of MALL in NSCLC |
Authors: | Yen Chun-Lai 賴彥君 |
Advisor: | 俞松良(Sung-Liang Yu) |
Keyword: | MALL,侵襲,轉移,致癌基因,非小細胞肺癌, MALL,Invasion,Migration,Oncogene,NSCLC, |
Publication Year : | 2011 |
Degree: | 碩士 |
Abstract: | 背景:先前的研究指出MALL可與Caveolin-1相互作用,至於Caveolin-1是一種已知的致癌基因,它可透過促進絲狀偽足的生成來促進肺腺癌細胞的侵襲能力,因此我們的目標為研究在臨床上MALL在非小細胞肺癌中表現量的高低是否與病人的預後相關,以及MALL是透過何種機制來影響癌症的進程。
方法:我們在MALL表現量較低的肺癌細胞中(CL1-0, NCI-H226, Hop62)過度表現MALL,以及在MALL相對表現量較高的肺癌細胞(CL1-5, A549)中抑制MALL的表現,藉由觀察體外細胞的不依賴支持物生長能力、生長速度、分解膠質能力、移動與侵襲能力,以及觀察老鼠體內的腫瘤生成能力。並且利用DNA微陣列晶片與即時定量聚合酶連鎖反應來探討MALL可能的下游基因,以協助我們釐清MALL主要透過何種訊息傳遞路徑來影響癌細胞的特性改變。另一方面,我們也藉由即時聚合酶連鎖反應來偵測臨床病人癌症組織中MALL的mRNA表現量,利用統計方法分析MALL的mRNA表現量在正常的組織與癌症組織中是否有差異,並且分析MALL m RNA表現量與臨床病人肺癌進展的關聯性。 結果:我們建立了大量表達MALL蛋白的系統來藉以探討此基因的功能,並且發現MALL可以促進肺癌細胞的侵襲能力,同時,無論使用傷口癒合移動實驗或是細胞移動分析皆可發現MALL促進肺癌細胞的移動能力,甚至MALL可以增加細胞不依賴支持物生長的能力,同樣的結果也可在老鼠腫瘤生成模式中得到證實。這些發現都指出MALL可以促進腫瘤的轉移能力以及生成能力。 結論:在我們的實驗中,我們觀察到MALL具有致癌基因的特性,MALL作為一可能的致癌基因,並且可能在臨床用藥及治療上提供嶄新的面向。 Background: Previous study showed that MALL can interact with Caveolin-1, and Caveolin-1 could enhance the invasive capability of lung adenocarcinoma cells by inducing filopodia formation. Therefore, we investigated the clinical significance of MALL expression in non–small-cell lung cancer (NSCLC) patients and its role in cancer progression. Methods: We enforced the expression of MALL in the cells with lower endogenous MALL expression (CL1-0, NCI-H226 and Hop62) and silenced MALL in those cells with higher endogenous MALL expression (CL1-5 and A549). The cell anchorage-independent growth, proliferation, cell migration, invasion, and in vivo turmorigenesis were analyzed in these transfectants. The potential downstream genes of MALL were identified by oligonucleotide microarray and quantitative reverse transcription–polymerase chain reaction (RT-PCR). In clinical correlation, we measured MALL expression in 90 tumor tissue of NSCLC patients by RT-PCR. Correlation between MALL expression and overall survival was determined by the log-rank test and multivariable Cox proportional hazards regression analysis. All statistical tests were two-sided. Results: We found that MALL can significantly enhance cancer invasiveness by the Boyden chamber matrigel assay (2.12 fold, p<0.01). MALL also promoted cell migration by the transwell assay (1.53 fold, p<0.01) and wound healing assay. Moreover, MALL increased the colonogenesis of lung cancer cells by using an anchorage-independent colony formation assay (1.79 fold, p<0.05) but did not affect the rate of cell proliferation by MTT assay. These findings indicated that MALL can promote tumor metastasis and tumorigenesis. Conclusion: MALL showed an oncogenic characteristic in NSCLC, and MALL might be a potential oncogene which might provide new insights into the future treatment of lung cancer. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/45886 |
Fulltext Rights: | 有償授權 |
Appears in Collections: | 醫學檢驗暨生物技術學系 |
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