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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 吳漢忠(Han-Chung Wu) | |
dc.contributor.author | Yi-Ping Wang | en |
dc.contributor.author | 王逸平 | zh_TW |
dc.date.accessioned | 2021-05-15T18:00:45Z | - |
dc.date.available | 2014-02-25 | |
dc.date.available | 2021-05-15T18:00:45Z | - |
dc.date.copyright | 2014-02-25 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-01-03 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/5498 | - |
dc.description.abstract | 背景:雖然近年來癌症治療方式有長足進步,晚期頭頸部鱗狀細胞癌之存活率依舊不佳。近年研究顯示,astrocyte elevated gene-1 (AEG-1)此一單次穿膜蛋白雖無任何已知之功能區段,但仍在多種人類癌症中高度表現並與轉移發生及較差之存活率相關。
結果:頭頸部鱗狀細胞癌中AEG-1之高度表現與區域淋巴結轉移及較差之五年存活率呈正相關。將頭頸部鱗狀細胞癌細胞株中之AEG-1敲減表現後,其細胞群落形成、移動、及入侵能力皆為下降。此外,AEG-1敲減表現後之頭頸部鱗狀細胞癌細胞株轉植於免疫不全小鼠中所形成的腫瘤體積及肺部轉移病灶亦皆減少。我們並發現AEG-1可上升NF-κB中p65次單元之磷酸化,進而調控頭頸部鱗狀細胞癌細胞表現MMP1酵素。同時頭頸部鱗狀細胞癌之臨床檢體AEG-1、磷酸化p65及MMP1之表現互相呈現統計上有意義之相關性。 結論: AEG-1於頭頸部鱗狀細胞癌中高度表現與淋巴結轉移相關,並為頭頸部鱗狀細胞癌臨床預後之負向指標。 | zh_TW |
dc.description.abstract | Background: The survival rate of head and neck squamous cell carcinoma (HNSCC) at advanced stage is poor, despite contemporary advances in treatment modalities. Recent studies have indicated that astrocyte elevated gene-1 (AEG-1), a single transmembrane protein without any known functional domains, is overexpressed in various malignancies and is implicated in both distant metastasis and poor survival.
Results: High expression of AEG-1 in HNSCC was positively correlated with regional lymph node metastasis and a poor 5-year survival rate. Knockdown of AEG-1 in HNSCC cell lines reduced their capacity for colony formation, migration and invasion. Furthermore, decreased tumor volume and metastatic foci were observed after knockdown of AEG-1 in subcutaneous xenografts and pulmonary metastasis assays in vivo, respectively. We also demonstrated that AEG-1 increased phosphorylation of the p65 subunit of NF-κB, and regulated the expression of MMP1 in HNSCC cells. Moreover, compromised phosphorylation of the p65 (RelA) subunit of NF-κB at serine 536 was observed upon silencing of AEG-1 in HNSCC cell lines and the expression status of AEG-1, phosphorylated p65 and MMP1 are mutually correlated in clinical specimens. Conclusion: High expression of AEG-1 is associated with lymph node metastasis and is a negative prognostic parameter for clinical outcome in HNSCC. Keywords: Astrocyte elevated gene-1 (AEG-1), head and neck squamous cell carcinoma (HNSCC), metastasis, matrix metalloproteinase 1 (MMP1), p65 | en |
dc.description.provenance | Made available in DSpace on 2021-05-15T18:00:45Z (GMT). No. of bitstreams: 1 ntu-103-D96422003-1.pdf: 4958911 bytes, checksum: 90c3aecbfa07660f1cdcd543c003d855 (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 口試委員會審定書 2
致謝 3 中文摘要Table of content 4 Abstract 5 Table of content 6 Chapter I: Introduction 9 1. Head and neck squamous cell carcinoma 9 2. Astrocyte elevated gene-1 10 2.1. Initial cloning and structure 10 2.2 Physiological expression profile 11 2.3 Regulation of expression 12 2.4 Downstream signaling pathway and interacting proteins 13 2.4.1 Nuclear factor-κB (NF-κB) 13 2.4.2 Phosphatidylinositol 3-kinase (PI3K/Akt) 15 2.4.3 Staphylococcal nuclease domain-containing 1 (SND1) 17 2.5 Roles in tumor invasion/metastasis 18 3. Specific aims 19 Chapter II: Materials and Methods 21 1. Clinical specimen acquisition and clinicopathological staging 21 2. Immunohistochemical staining 21 3. Cell lines 23 4. WST-1 assays 24 5. Colony formation assays 24 6. Migration assays and transwell Matrigel invasion assays 24 7. Western blot analysis 25 8. In vivo xenograft tumor assays 26 9. In vivo pulmonary metastasis assay 27 10. Microarray analysis 27 11. Real-time quantitative polymerase chain reaction 28 12. Immunogold labeling and transmission electron microscopy 29 13. Flow cytometry 29 14. Luciferase assay of the MMP1 promoter region 30 15. Chromatin immunoprecipitation (ChIP) assay 31 16. Statistical analysis 32 Chapter III: Results 33 1. High AEG-1 expression in OSCC is associated with regional lymph node metastasis and unfavorable 5-year survival 33 2. AEG-1 knockdown reduced the aggressiveness of HNSCC cell lines in vitro 34 3. AEG-1 knockdown reduces tumor volume and pulmonary metastatic nodules of HNSCC cell lines in vivo 35 4. AEG-1 suppression downregulates MMP1 production 36 5. AEG-1 expression increases phosphorylation of the p65 subunit of NF-κB and enhances p65 binding to the MMP1 promoter 37 Chapter IV: Discussion 41 Chapter V: Conclusion 51 Acknowledgement 52 References 53 Figures 64 Tables 79 Appendix 83 A. Curriculum Vita 84 B. Published article 85 | |
dc.language.iso | en | |
dc.title | AEG-1/LYRIC 於頭頸部鱗狀細胞癌中生物功能之研究 | zh_TW |
dc.title | Study of Biological Functions of AEG-1/LYRIC in Head and Neck Squamous Cell Carcinoma | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-1 | |
dc.description.degree | 博士 | |
dc.contributor.coadvisor | 江俊斌(Chiung-Pin Chiang) | |
dc.contributor.oralexamcommittee | 靳應台(Ying-Tai Jin),張龍昌(Lung-Chang Chang),廖永豐(Yung-Feng Liao) | |
dc.subject.keyword | Astrocyte elevated gene-1 (AEG-1),頭頸部鱗狀細胞癌 (HNSCC),轉移,基質金屬蛋白?1 (MMP1),p65, | zh_TW |
dc.subject.keyword | Astrocyte elevated gene-1 (AEG-1),head and neck squamous cell carcinoma (HNSCC),metastasis,matrix metalloproteinase 1 (MMP1),p65, | en |
dc.relation.page | 84 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2014-01-03 | |
dc.contributor.author-college | 牙醫專業學院 | zh_TW |
dc.contributor.author-dept | 臨床牙醫學研究所 | zh_TW |
顯示於系所單位: | 臨床牙醫學研究所 |
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