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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳青周(Ching-Chow Chen) | |
| dc.contributor.author | Chu-Fang Liu | en |
| dc.contributor.author | 劉竹芳 | zh_TW |
| dc.date.accessioned | 2021-06-13T00:24:48Z | - |
| dc.date.available | 2016-10-07 | |
| dc.date.copyright | 2011-10-07 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-04 | |
| dc.identifier.citation | Adli, M., Zhu, J. and Bernstein, B. E. (2010). 'Genome-wide chromatin maps derived from limited numbers of hematopoietic progenitors.' Nat Methods 7(8): 615-618.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/28829 | - |
| dc.description.abstract | 肝癌為全球第五大常見癌症，惡性度極高且病程進展快速，為癌症相關死亡之第三位。許多文獻證實，肝癌腫瘤長期處於低氧環境，導致HIF1累積與活化，促使癌細胞增生且抑制凋亡。此外，低氧環境降低DNA之修復能力，致使DNA斷裂和累積genomic instability，增加癌細胞之mutagenesis和chromatin remodeling
；低氧亦能誘發Epithelial-Mesenchymal Transistion，mesenchymal form之細胞具cancer stem cell之特性。有報導指出，AID在in vitro會deaminate Oct3/4與Nanog之5’-methyl-cytidine，間接造成DNA demethylation而使細胞呈現幹細胞之特性；在肝癌病人之病理切片有AID之過度表現。本實驗中，除了發炎環境外，低氧環境透過穩定HIF1，會增加肝癌細胞 (HepG2) AID之mRNA表現，在人類肺腺癌上皮細胞株A549亦有相同結果。以基因轉殖法於HepG2細胞大量表現HIF1α，亦可引發AID之表現；knock down AID則抑制HIF1α所誘發的Oct3/4和SOX2表現，表示AID是低氧環境中誘導Oct3/4和SOX2表現所必須。在過度表現AID之HepG2細胞中，vimentin和N-cadherin之表現增加、wound healing能力提升，以及有MAPK和PI3K/AKT活化現象。因此，低氧環境可誘發AID之mRNA和protein表現，進而誘發Oct3/4和SOX2在肝癌細胞之表現、提升wound healing ability，並且增加MAPK和AKT之磷酸化，顯示AID在肝癌惡性度和病程進展可能具重要角色。 | zh_TW |
| dc.description.abstract | Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Featured by rapid progression and high malignancy, HCC ranks the third leading cause of cancer-related death. It is evidenced that its tumor mass is chronically under hypoxia, which causes the accumulation and activation of HIF1α and subsequently stimulates tumor proliferation and inhibits apoptosis. Additionally, hypoxia attenuates DNA repair system, which causes DNA double strand breaks and the accumulation of genetic instability. Hypoxia also causes Epithelial-Mesenchymal Transition that renders cells possess cancer stem cell property. Recently, AID is reported to indirectly initiate DNA demethylation of Oct3/4 and Nanog promoter by deamination of 5’-methyl-cytidine. In surgical resected HCC tissues, AID was significantly over-expressed. In this study, we pointed out that hypoxic microenvironment could induce the expression of AID via HIF signaling in HCC cell lines and A549 cells. Similar result was seen while over-expressing HIF1α in HepG2 cells. Knock-down of AID inhibited HIF-induced Oct3/4 and SOX2 expression, indicating that AID is required for hypoxia-induced Oct3/4 and SOX2 expression. In HepG2 cells over- expressing AID, we observed the increasing expression of vimentin and N-cadherin, enhanced wound-healing ability, and the activation of p-ERK and p-Akt, suggesting that AID might be related to the rapid progression and high malignancy of HCC. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T00:24:48Z (GMT). No. of bitstreams: 1 ntu-100-R98443011-1.pdf: 4593395 bytes, checksum: 5f1020d2bd8c487456ad920af931b523 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | Chapter І. Introduction 1
Section 1. Hepatocellular carcinoma (HCC) 1 Epidemiology 1 Risk factors and pathogenesis of HCC 2 Tumor staging and therapies 5 Section 2. Hypoxia 13 Tumor biology under hypoxia 13 HIF signaling 14 Tumor responses to hypoxia 15 Section 3. Activation-induced cytidine deaminase (AID) 37 The structure and biological function of AID 37 AID-dependent DNA demethylation 38 The significant role of AID in cancers 39 Section 4. Cancer Stem Cells (CSCs) 47 Definition and hypotheses of CSC 47 Mechanism of reprogramming towards pluripotency 48 Identification of CSCs in tumor cells 51 Relationship between CSCs and EMT 53 Study Motivation 60 ChapterⅡ. Materials and Methods 61 ChapterШ. Results 69 ChapterⅣ. Discussion 91 ChapterⅤ. Conclusion 96 References 97 | |
| dc.language.iso | en | |
| dc.subject | 低氧 | zh_TW |
| dc.subject | EMT | en |
| dc.subject | AID | en |
| dc.subject | hypoxia | en |
| dc.title | 低氧環境誘導之AID在EMT角色之研究 | zh_TW |
| dc.title | Studies of Hypoxia-Induced AID and Its Role in EMT | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 吳明賢(Ming-Shiang Wu),黃偉謙(Wei-Chien Huang) | |
| dc.subject.keyword | 低氧, | zh_TW |
| dc.subject.keyword | hypoxia,AID,EMT, | en |
| dc.relation.page | 113 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2011-08-05 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥理學研究所 | zh_TW |
| 顯示於系所單位： | 藥理學科所 | |
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