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Title: | 在肝臟中專一性過量表現第二型類胰島素因子將導致肝臟不正常的增生 Liver-Specific Overexpression of igf-2 Leads to Liver hypertrophy |
Authors: | Yu-Da Chen 陳昱達 |
Advisor: | 吳金冽 |
Keyword: | 第二型類胰島素因子,肝癌, igf-2,Liver hypertrophy, |
Publication Year : | 2005 |
Degree: | 碩士 |
Abstract: | 中文摘要
第二形類胰島素因子 (IGF-II),是刺激細胞分裂分化的一個重要的原素,且在胚胎發育上扮演一個重要的角色。大部分的IGFs由肝臟生產藉由與類胰島素因子結合蛋白(IGFBPs)構成一個複合蛋白然後釋放到血液中在生物體內循環。在先前的研究中指出,IGF-2通常會被基因印痕(genomic imprinting)抑制其表現。但是,IGF-2經常由腫瘤和腫瘤細胞株所分泌,尤其是在肝癌中,在肝臟硬化的早期機制中,通常會伴隨著IGF-2表現量的增加,特別是在由HBV和HCV引起的慢性肝癌。由於IGF-2的大量表現與肝癌的發生有著相當密切的關係,所以本篇論文嘗試設計在斑馬魚的肝臟中過量表現IGF-2,並針對其下游因子以及受到過量表現IGF-2影響的肝臟的型態加以分析。 在結果中發現,過量表現IGF-2 將引起肝臟異常肥大,而且細胞的型態也與對照組不同,在分析其下游基因後發現,抗細胞凋亡基因群及促細胞週期基因群都會受到IGF-2的正調控,從這些的結果中指出,在肝臟中過量表現IGF-2極有可能可以發展成肝癌。在將來的實驗上可以利用這樣的轉殖基因魚,使其成為一個易於誘發肝癌的疾病模式。 Abstract Insulin-like growth factor-2 (IGF-II), mainly synthesized in liver then transport to target tissues through endocrine system, is an important factor that stimulate cell proliferation, differentiation and division, promote organ development and play as a survival factor in apoptosis. However, the functional role of liver-derived IGF-II before partum still remains unclear. In this study, we use liver fatty acid binding protein (L-FABP) promoter to drive IGF-II expression in a liver-specific manner. To facilitate the direct imaging of liver development, constructs containing expression cascade were introduced to one-cell stage embryo of transgenic zebrafish lines bearing liver-specific GFP expression. Exogenous IGF-2 expression is first detected at 34hpf under the control of LFABP promoter. Obvious liver enlargement was observed at 10dpf and continues to grow; gut tube was pushed up by the enlarged liver but appears un-disrupted morphologically. At 17dpf, the volume of IGF-2 over-expressed liver is 1.5 times bigger statistically than the wild-type control using confocal microscopy. The increased number and enlarged hepatocyte cell shape were also observed under confocal microscopy examination. We further use PT-PCR to monitor molecular, which may involve in this phenomena. IGF-binding protein, IGFBP1 and IGFBP3 were down-regulated; Cell cycle related gene such as c-myc, cyclin-D1, gankyrin; anti-apoptosis genes such as bcl-xl and liver-enriched transcription factors such as HNF4αand HNF1αwere up-regulated suggesting the rapid cell division leading to increase cell number were controlled by hepatic program and anti-apoptosis genes. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/34952 |
Fulltext Rights: | 有償授權 |
Appears in Collections: | 漁業科學研究所 |
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ntu-94-1.pdf Restricted Access | 1.59 MB | Adobe PDF |
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