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標題: | 肝臟專一性表現 HBx 促進斑馬魚模式生物肝癌的形成 Liver specific and inducible expression of HBx promote tumorigenesis in zebrafish |
作者: | Chien-Yuan Lin 林健淵 |
指導教授: | 吳金洌(Jen-Leih Wu) |
關鍵字: | X 蛋白,肝細胞癌,活體觀測,四環黴素誘導系統,肝臟疾病模式動物, HBx,HCC,in vivo imaging,Tetracycline-inducible system,liver disease, |
出版年 : | 2009 |
學位: | 碩士 |
摘要: | Hepatitis B virus (HBV) X protein (HBx) can transactivate proto-oncogene, induce protein kinase signaling pathway and interact with numerous cellular protein, as p53 and hTRET. Studies all showed the potential role of HBx to promote HBV-related hepatocellular carcinoma (HCC); however, the role of HBx play in the pathogenesis of HCC is still enigma. Some reports suggested there is a threshold level of HBx in HCC development. The rapid degradation of HBx by the proteasome pathway, which is one character of HBx protein, will lead to the low concentration of HBx. By the way, there are also inconsistent data in both in vitro result and HBx transgenic mouse in vivo models. Conditional expression system (Tetracycline (Tet)-inducible) is adopted to highly and specifically express HBx in the liver of zebrafish, here, we try to reveal the role of HBx in liver pathology and also reflect to the high level of HBx in the clinical case. We established a liver disease model by using zebrafish and explained the possible mechanism of HBx involved in pathogenesis of HCC, from the hepatocyte apoptosis to the liver disease progression. For performance of the Tet-inducible system in vivo, we first tested the toxicity of doxycycline (Dox) in zebrafish and 100μg/ml is highest dosage for induction without severe toxicity. Later, 30μg/ml is chosen as the default concentration for the induction assay and the inducible expression pattern is successfully and efficiently achieved in our in vivo model. In the liver pathology, human liver disease progression, as inflammation, fibrosis and HCC phenotype, can also be observed in the transgenic zebrafish by using H&E staining. By the induction of TGF-β expression in the liver, we hypothesis the apoptotic capacity of HBx may play an important role in the HBV- related liver disease progression. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/23123 |
全文授權: | 未授權 |
顯示於系所單位: | 微生物學科所 |
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