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研究生: 張竣偉
Chang, Chun-Wei
論文名稱: CapG於口腔癌所扮演的角色
The role of CapG in oral cancer progression
指導教授: 陳玉玲
Cheng, Yuh-Ling
學位類別: 碩士
Master
系所名稱: 醫學院 - 口腔醫學研究所
Institute of Oral Medicine
論文出版年: 2011
畢業學年度: 99
語文別: 中文
論文頁數: 52
中文關鍵詞: 口腔癌細胞增生
外文關鍵詞: CapG, oral cancer, proliferation
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  • CapG為gelsolin家族的actin filament capping protein,又稱為macrophage capping protein。在過去的文獻中顯示CapG於癌細胞中具有侵犯及轉移的能力,但是也有人提出不同的意見:他們認為CapG具有降低腫瘤形成的能力。因此到目前為止CapG與腫瘤惡性轉變的關係並無一個統一的論點。由於對於CapG在癌症細胞中所扮演的角色並不明確,因此我們想針對CapG在口腔癌形成所扮演的角色來進行探討。我們利用50個口腔鱗狀細胞癌 (OSCC)檢體進行即時定量 polymerase chain reaction (QPCR)實驗,實驗結果顯示CapG表現對於初期腫瘤大小具有高度相關性。我們也將40個口腔鱗狀細胞癌 (OSCC)檢體利用免疫組織化學染色法 (IHC)進行觀察CapG於腫瘤組織中高度表現的位置及細胞形態,研究發現CapG高度表現於惡性程度較高之檢體中。在細胞實驗中,當抑制CapG的表現於 HSC-3 and SCC-15細胞株時會抑制其增生的能力;而過度表現CapG在 OEC-M1 and OC-2細胞株時則會增加細胞增生的能力。但不論過度表現或抑制CapG的表現卻皆不會影響其細胞移行的能力。此外利用皮下注射的方式將口腔癌細胞打入免疫缺陷老鼠後發現,打入抑制CapG表現的細胞株相較於對照組在老鼠體內會有體積較小的腫瘤形成。總觀上述實驗發現,CapG在口腔癌腫瘤形成中扮演了非常重要的角色,而對於移行及侵犯能力則不造成影響。此研究可釐清CapG在口腔癌所扮演的角色及其作用機轉,且在未來有可能可以成為新的診斷及治療標靶。

    CapG is an actin filament capping protein of the gelsolin family, also known as macrophage capping protein. Previous evidence have indicated that CapG possesses an oncogenic function involved in the control of cell migration or invasion, but other investigators showed that CapG protein expression reduces the ability of a transformed cell to induce tumor formation, suggesting that CapG is a tumor suppressor gene. Oral squamous cell carcinoma (OSCC) is one of most common neoplasms worldwide and the 4th leading neoplasm and fastest growing cancer in Taiwanese males. The aim of the present study was to clarify the expression levels of CapG in well-classified specimens from clinical OSCC patients and to realize the functional role of the CapG in oral cancer progression. First we analyzed the mRNA expression of CapG in 50 oral cancer samples by quantitative real-time polymerase chain reaction analyses (QPCR), and we found that the CapG expression were significantly positively correlated with primary tumor volume. We further used immunohistochemistry (IHC) to examine the expression pattern of the CapG proteins in 40 OSCC samples. CapG expression was significantly higher in the high AJCC tumor stage. Knockdown of CapG in HSC-3 and SCC-15 cells decrease the ability of proliferation, and overexpression of CapG increased proliferation rate in OEC-M1 and OC-2 cells. In spite of changing the CapG expression in oral cancer cells has no effect on cell migration. Moreover, CapG-silenced oral cancer cells formed smaller xenograft tumours than did control cells. Taken together, CapG plays an important role in oral cancer tumorigenesis, but not in cancer cell motility. This result clarify the role of CapG in oral cancer progression and its biological mechanism, and hope this could be a new prognosis marker and therapeutic target of oral cancer in the future.

    中文摘要……………………………………………………………………... I 英文摘要……………………………………………………………………. III 致謝………..…………………………………………………………………. V 目錄…………………………...……………………………………………… VII 表目錄…………………………...………………………………………….... IX 圖目錄......…………………………………………...…………………..…… X 緒論…………………………………………………………………………... 1 1. 口腔癌…………………….……………………………...……………. 1 2. CapG-肌動蛋白絲被帽蓋蛋白……………….............……………. 2 3. CapG的作用…………………………………………………….….…. 2 4. Gelsolin家族與癌症的關係……………...………….…….…….….… 3 5. CapG在癌症上扮演的角色………………………………………….. 3 6. CapG於細胞中作用的位置………………………………………….. 4 研究動機……………………………………………….….….………….…... 5 材料與方法………………………………….…………….….………….…... 6 實驗結果……………………………………………………….…………….. 24 ㄧ、 臨床口腔鱗狀上皮細胞癌組織中CapG的表現量與口腔癌初期腫瘤大小具有正相關性…………………….………………………. 24 二、 利用免疫組織染色法發現腫瘤惡性程度與其CapG表現量具有高度的相關性,但與CapG表現於口腔癌細胞位置並不相關… 24 三、CapG在口腔癌細胞株中protein表現量……………………..……… 25 四、CapG在口腔癌細胞中與細胞增生能力具正相關性………..…...…. 26 五、CapG改變對口腔癌細胞的移行能力不造成影響…………….…… 26 六、CapG主要表現在口腔癌細胞其細胞質及細胞核中………………... 26 七、 在動物實驗中發現CapG的改變與腫瘤所形成的大小具有正相關. 27 八、在動物實驗中抑制CapG的表現會抑制其腫瘤組織增生的能力....... 27 討論……………………….……………..……………..…………………….. 29 結論…………………….…………….……..………………………………... 34 參考文獻……….….………………….………..…………………………….. 35 附錄一:儀器…………………………………………………………............. 50 附錄二:英文縮寫……………………………………...……..……................ 51 自述……………………….…………………………………..……................ 52

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