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研究生:張勁柳
研究生(外文):Chin-Liew Chong
論文名稱:探討UK114蛋白在肝癌癌化過程之角色
論文名稱(外文):Investigation of the role of UK114 in hepatocellular carcinogenesis
指導教授:張仲明
指導教授(外文):Chung-Ming Chang
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:微生物及免疫學研究所
學門:生命科學學門
學類:微生物學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:62
中文關鍵詞:原發性肝細胞癌
外文關鍵詞:primary hepatocellular carcinomaHCCUK114
相關次數:
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原發性肝細胞癌(primary hepatocellular carcinoma, HCC)是世界上最常見的惡性腫瘤之一。然而,就其病原學上及其分子層面的致病機轉仍不清楚。分析正常肝細胞及肝癌細胞之間基因表現的差異,將有助於鑑定與其致病機轉有關的因子。本論文中,發現UK114,一個主要在肝臟細胞及腎臟細胞中大量表現的蛋白質,其表現量在肝細胞癌組織中有明顯減低的現象,同時其表現量亦隨著癌細胞分化程度變差而下降。此下降情形也同樣出現在HuH7、HepG2及 Hep3B等肝癌細胞株中。在以HepG2或HuH7所建立之UK114的穩定細胞株,似乎具有抑制腫瘤細胞在裸鼠內的腫瘤生成能力。此外,UK114之表現亦會降低細胞株之群落生長能力。但是,大量表現UK114,無法減低HepG2及HuH7細胞之生長速率,及改變HuH7之細胞週期。同時,我們也對UK114的調控加以分析,結果發現UK114的表現似乎不受到其基因體上去氧核糖核酸甲基化(DNA methylation),或是組織蛋白的去乙醯化(histone deacetylation)的影響。因此,UK114在肝癌細胞表現量減少的調控機制目前尚不清楚。總而言之,在近70%的HCC檢體中UK114之表現量均是下降的,而且其表現量與腫瘤之分化程度相關,雖然,UK114不會抑制細胞之生長速率,但會減低肝癌細胞的群落生成及在裸鼠之生長,可見UK114在肝癌之產生及癌化之過程中扮演著重要的角色。
Primary hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the precise molecular mechanisms of HCC pathogenesis are not clear. The comparison of gene expression profiles between primary normal human hepatocytes and primary hepatocellular carcinoma may yield some potential factors that contribute to the pathogenesis of HCC. In this thesis, we found that UK114, a 14.5 kD protein primarily found in liver and kidney, is significantly down-regulated in tumor tissue of HCC as compared to the adjacent normal tissue. Furthermore, the expression level of UK114 is shown to be correlated with the differentiation grade of HCC tissue. Normally, the UK114 expression level in HCC tumor cell lines, such as HepG2, HuH7 and Hep3B, is relatively low. Stable clones of HepG2 and HuH7 that express UK114 seems to have reduced tumorigenicity in vivo and the expression of UK114 is associated with the colony forming activity in vitro. However, the expression of UK114 does not alter the proliferation rate of the cell line in both stable clone and transient transfection model nor it affects the cell cycle patterns of the cell lines. We also investigate mechanism involved in the regulation of UK114 in HCC cell lines. Although our data does not provide a clear mechanism, it does not support the hypothesis that down-regulation of UK114 is mediated by hypermethylation or histone deacethylation. In summary, a large portion of HCC specimens show down-regulation of UK114, and the expression level correlated with the grade of the HCC. Even though over-expression of UK114 has no effect on cell growth, it reduced the in vitro colony forming activity and the in vivo tumorigenecity of the cell lines. We conclude that UK114 might play an important role in hepatocellular carcinogenesis.
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