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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 鄭永銘 | |
dc.contributor.author | Hsin-Jung Lee | en |
dc.contributor.author | 李幸容 | zh_TW |
dc.date.accessioned | 2021-06-16T23:56:49Z | - |
dc.date.available | 2014-09-18 | |
dc.date.copyright | 2012-09-18 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-07-18 | |
dc.identifier.citation | 1. El-Serag, H.B. and K.L. Rudolph, Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology, 2007. 132(7): p. 2557-76.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65659 | - |
dc.description.abstract | 肝細胞癌(HCC)是台灣最普遍的致命癌症之一,截至目前為止除了蕾莎瓦(Sorafenib)以外,尚未找到其他有效的治療方法。而在癌症的標靶治療中,最常見的就是針對受器酪胺酸激脢(RTK)的抑制,因此,在肝細胞癌的受器酪胺酸激脢中找出標靶治療的新標的就顯得更為重要了。經由受器酪胺酸激脢陣列試驗(RTK array),我們發現Axl在肝癌細胞中是常被活化的受器酪胺酸激脢之一,而在之前的報導都提到過在許多的癌症中Axl的活化會增加腫瘤侵犯能力,然而其中的機制尚未完全被瞭解。在本篇實驗中,Axl的基因敲減會抑制肝細胞癌細胞侵犯能力,而給予Axl的配體Gas6會提高細胞的侵犯能力。此外,我們發現促進上皮間質轉化的轉錄因子Slug,會被Gas6/Axl誘導表現,Gas6會活化PI3K/Akt 和 MAPK路徑。在肝細胞癌細胞株中給予MAPK 路徑的抑制劑PD98059會抑制Gas6引起的Slug的表現,Axl的抑制物Bosutinib會抑制肝細胞癌細胞株的侵犯能力,這證實了Gas6/Axl是經由MAPK 路徑增加Slug轉錄來調控癌細胞侵犯能力。 | zh_TW |
dc.description.abstract | Hepatocellular carcinoma (HCC) is one of the most common fatal cancers in Taiwan. Until now, no effective systemic therapy is available, except for the sorafenib treatment. Most targets of molecularly targeted therapy for cancer are receptor tyrosine kinases (RTKs). Therefore, identification of activated RTKs in cancer is of ultimate importance in identifying new targets for molecularly targeted therapy. Using RTK array, we found that Axl is one of the most frequently activated RTKs in liver cancer cell lines. Activation of Axl has been reported to enhance tumor invasion in several types of human cancer; however, the mechanism is still unknown. The results in this study showed that knockdown of Axl by RNA interference significantly reduced cell invasion in HCC cell lines HA22T and Mahlavu. On the other hand, treating cells with Axl ligand Gas6 enhanced tumor invasion. We identified epithelial-mesenchymal transition (EMT)-inducing transcription factor Slug as one of the targets of Gas6/Axl pathway. PI3K/Akt pathway and MAPK pathway were activated by Gas6 treatment. Treating HCC cell line HA22T with the MAPK pathway inhibitor PD98059 suppressed the induction of Slug by Gas6. Axl inhibitor Bosutinib decreased the invasiveness of HCC cell lines. These results suggest that Gas6/Axl regulates tumor invasion via transcriptional activation of Slug by MAPK pathway. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T23:56:49Z (GMT). No. of bitstreams: 1 ntu-101-R99444007-1.pdf: 1995195 bytes, checksum: 6b824272853e0abda660ec6de6b36af7 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | CHAPTER PAGE
口試委員會審定書 I 謝辭 II 中文摘要 III ABSTRACT IV I INTRODUCTION 1 1.1 Hepatocellular carcinoma 1 1.2 Receptor tyrosine kinase 1 1.3 Gas6 2 1.4 Axl 3 1.4.1 Signaling transduction pathway of Gas6/Axl 4 1.4.2 Expression Gas6/Axl in cancer 5 1.4.3 Axl and tumor proliferation 7 1.4.4 Axl and tumor invasion 7 1.4.5 Angiogenesis 8 1.4.6 Axl and drug resistance 9 1.4.7 Axl and immunity 9 1.4.8 Axl and epithelial-mesenchymal transition 10 1.5 Slug 10 1.6 Aims of the study 11 II MATERIALS AND METHODS 12 2.1 Materials 12 2.2 Cell culture 12 2.3 RTK array 12 2.4 RNA interference 13 2.5 RNA isolation 14 2.6 RT-PCR 14 2.7 Western Blot 14 2.8 In vitro Boyden Chamber Invasion Assay 15 2.9 Wound healing assay 16 III RESULTS 17 3.1 Axl is frequently activated and expressed in HCC cell lines 17 3.2 Knockdown of Axl suppresses cell invasion and migration 17 3.3 Gas6 stimulates phosphorylation of Axl and induces cell invasion 18 3.4 Induction of Slug expression in HA22T by Gas6 18 3.5 Both PI3K/Akt pathway and MAPK pathway are activated by Gas6 treatment 18 3.6 Erk inhibitor (PD98059) suppresses Slug expression and cell invasion 18 3.7 Bosutinib (SKI-606) suppresses Slug expression and cell invasion 19 IV DISCUSSION 20 V FIGURES AND TABLES 23 5.1 Tables 23 5.2 Figures 26 REFERENCES 36 | |
dc.language.iso | en | |
dc.title | Gas6/Axl途徑在肝細胞癌中經由Slug調控腫瘤侵犯 | zh_TW |
dc.title | Gas6/Axl regulates tumor invasion via slug in hepatocellular carcinoma | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 許金玉,連晃駿,張正琪 | |
dc.subject.keyword | 肝細胞癌,Gas6,Axl,Slug,侵犯, | zh_TW |
dc.subject.keyword | Hepatocellular carcinoma (HCC),Gas 6,Axl,Slug,invasion, | en |
dc.relation.page | 43 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-07-18 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 病理學研究所 | zh_TW |
顯示於系所單位: | 病理學科所 |
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