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研究生:黃兆清
研究生(外文):Chao-Ching Huang
論文名稱:Aurora-A基因轉殖小鼠之肝臟病理分析
論文名稱(外文):Liver Pathogenesis of the Aurora-A Transgenic Mice
指導教授:蔡亭芬
指導教授(外文):Ting-Fen Tsai
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:遺傳學研究所
學門:生命科學學門
學類:生物訊息學類
論文種類:學術論文
論文出版年:2006
畢業學年度:94
語文別:中文
論文頁數:51
中文關鍵詞:肝癌轉殖小鼠
外文關鍵詞:Aurora-A
相關次數:
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  • 點閱點閱:171
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Aurora-A目前在很多人類癌症中都會發現到過度表現的狀態,因為它的過度表現會產生非常數染色體性 (aneuploidy)、中心體數量異常以及在人類和老鼠細胞株內都會促使癌化的產生,但是到底是怎樣的機轉和病理變化由Aurora-A促使朝癌化的方向目前仍不知道,實驗室製造了Aurora-A的轉殖小鼠,想要瞭解因為Aurora-A過度表現在肝臟病理及癌化上的改變,在15個月大到20個月大年紀的轉殖小鼠,發現到肝臟退化 (liver degeneration)的病理,包含輕微的脂肪肝 (microsteatosis or macrosteatosis)、多型性的核仁 (Pleomorphic and bizarre nuclei)、膨大的肝細胞 (Ballooning of hepatocyte)、不正常排列的血管竇 (Abnormal arrangement of sinusoid)、發炎反應 (Inflammation),其腫瘤的發病率在轉殖小鼠上很低,只有7.7%,從病理的角度觀看為增生性的腫瘤還不到惡性的程度。並且從其蛋白質和RNA的表現上發現到轉殖基因的表現在2-3月下降,其他關於細胞週期和肝臟功能相關性的基因的表現還在研究,根據我們的研究,Aurora-A是個低度遺傳特質表現頻度腫瘤易感性基因 (low-penetrance tumor-susceptibility gene),並且在我們轉殖小鼠中單靠它並不能造成肝癌。
Aurora-A was reported to be overexpressed in various human cancers, and its overexpression induces aneuploidy, centrosome amplification and tumorigenic transformation in cultured human and rodent cells. However, the underlying mechanisms and pathological settings by which Aurora-A promotes tumorigenesis are largely unknown. We have generated a transgenic mouse model to investigate the involvement of Aurora-A overexpression in the development of liver pathogenesis and tumorigenesis. Liver degerneration including fatty change (microsteatosis or macrosteatosis), pleomorphic and bizarre nuclei, ballooning of hepatocyte, and abnormal arrangement of sinusoid was detected in the Aurora-A transgenic mice from 15 to 20 months of age. Low incidence of tumor formation was observed in the Aurora-A transgenic mice. Pathogenesis analysis indicated that the tumors were hyperplasia nodules without malignant characteristics. We found that there was a decrease of Aurora-A transgene expression around 2-3 months of age based on RNA and protein analysis. Molecular analysis of gene regulation of Aurora-A transgene, cell cycle genes, and liver function related genes is currently under investigation. Our results indicate that Aurora-A is a low-penetrance tumor-susceptibility gene, and by itself is not sufficient to cause liver cancer formation in the Aurora-A transgenic mice.
中文摘要……………………………………………………………4
英文摘要……………………………………………………………5
壹、緒論…………………………………………………………6~10
貳、材料與方法…………………………………………………11~21
參、結果…………………………………………………………22~25
肆、討論…………………………………………………………26~28
伍、參考資料……………………………………………………29-34
陸、表格…………………………………………………………35
柒、附圖…………………………………………………………36-51
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