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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 游偉絢 | |
dc.contributor.author | Hsing Kao | en |
dc.contributor.author | 高興 | zh_TW |
dc.date.accessioned | 2021-06-15T11:26:44Z | - |
dc.date.available | 2021-08-26 | |
dc.date.copyright | 2016-08-26 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-08-18 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49395 | - |
dc.description.abstract | The over-expression of epidermal growth factor receptor (EGFR) has been observed in many cancer types including lung carcinoma. Since EGFR signaling significantly enhances cell growth and survival, several EGFR tyrosine kinase inhibitors (TKI) have been developed to specifically shut down EGFR signaling pathway. However, drug resistance occurs in most cases resulting from the secondary EGFR mutations. TKI-resistant EGFR mutation has been the major problem against TKI-based therapy. Since EGFR activation promotes tumor survival and proliferation, elevated energy supply must be achieved to meet such activities. Previous studies in our lab had found that the direct over-expression of MMP7 can induce mitochondria proliferation. To find the upstream regulator of MMP7, in this thesis we observed that the amount of MMP7 and mitochondria increased after EGF stimulation in NSCLC cell line CL1-0. Different EGFR mutants also possessed different mitochondria induction abilities, and the levels of MMP7 expression were also proportional to mitochondria content. Based on these findings, we treated these cell lines with the mitochondria ATP synthase inhibitor citreoviridin to see the cell viability differences. As expected, cells with higher mitochondria abundancy were more sensitive to citreoviridin, implying that the induction of mitochondria proliferation by EGFR may shift the cell metabolism status to be more mitochondria-dependent. In this study, we established a positive relationship between EGFR, MMP7 and mitochondria and also provided an energy point of view toward EGFR related cancer treatment. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T11:26:44Z (GMT). No. of bitstreams: 1 ntu-105-R02442016-1.pdf: 1555422 bytes, checksum: 05ad39198b3296fb02af6d13769dda51 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 口試委員會審定書 #
誌謝 #2 中文摘要 i ABSTRACT i CONTENTS ii Chapter 1 Introduction 1 1.1 Matrix metalloproteinase and cancer development………….………………..1 1.2 The role of EGFR signaling pathways in lung carcinoma………………2 1.3 EGFR intracellular trafficking and cell surface shedding...........................3 1.4 EGFR mutations and lung cancer development………………………...…5 1.5 Clinical studies about tyrosine kinase inhibitors resistance………………5 1.6 New concept about mitochondria in tumor metabolism……….……….…6 1.7 Rationale to study the relationship between EGFR and mitochondria……….……….8 Chapter 2 Material and Methods 10 2.1 Experimental procedures 10 2.1.1 Plasmid preparation 10 2.1.2 Cell culture. 10 2.1.3 Site-directed mutagenesis. 10 2.1.4 Transfection. 11 2.1.5 Flow cytometry. 12 2.1.6 Western blot. 12 2.1.7 RT-PCR. 13 2.1.8 Cell viability assay. 13 2.1.9 ATP assay…………………………………………………………….14 2.1.10 Mitochondria isolation……………………………………………...15 2.1.11 Nucleus isolation…………………………………………………....15 2.1.12 Immunofluorescence staining……………………………………....16 2.2 Experimental material 17 2.2.1 Enzyme. 17 2.2.2 Kits. 17 2.2.3 Instruments and software. 17 2.2.4 Chemicals and reagents. 18 2.2.5 Media, solutions and buffers. 20 Chapter 3 Results 23 3.1 Mitochondria proliferation stimulated by EGF 23 3.2 Immunoblot and PCR analysis of VDAC and MTND1 expression for mitochondria proliferation induced by EGF 23 3.3 MMP7 expression also responses to EGF stimulation…….……….......24 3.4 Fluorescence microscope images showed differences of mitochondria abundancy between cells carrying different EGFR mutants…………..…...25 3.5 Immunoblot analysis for EGFR expression status of the cells carrying different EGFR mutants…………………………….…..………………….26 3.6 Immunoblot and PCR analysis for mitochondria abundancy of the cells carrying different EGFR mutants…………………………………………..27 3.7 Immunoblot analysis showed unequal MMP7 expression of the cells carrying different EGFR mutants…………………………………………..27 3.8 ATP concentration was higher in cells carrying more mitochondria…..…..28 3.9 MTT assay showed that citreoviridin imposed higher toxicity against cells with more abundant mitochondria………………………………….29 3.10 SRB assay confirmed the MTT assay results………………….…………30 3.11 Immunofluorescence staining images revealed different impacts on mitochondria by citreoviridin…………………………………………….31 3.11.1 Mitochondria of CL1-0 were non-affected……………………….32 3.11.2 Mitochondria of CL1-0 EGFRWT were mildly affected……….…32 3.11.3 Mitochondria were strongly fragmented in CL1-0 EGFRT790M, L858R………………………………………….32 3.11.4 Mitochondria were significantly fragmented in H1975………….32 3.12 Immunoblot analysis for mitochondria extract revealed EGFR localization……………………………………………………………...33 3.13 Immunoblot analysis for nuclear extract revealed EGFR localization…34 Chapter 4 Disccussion 35 REFERENCES 45 FIGURES……………………………………………………………………………….50 | |
dc.language.iso | en | |
dc.title | 以能量觀點探討表皮生長因子受體之活化對粒線體增生以及癌細胞存活之影響 | zh_TW |
dc.title | An energy point of view towards the effect of EGFR stimulation on mitochondria proliferation and cancer cell survival | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林敬哲,黃奇英,蔡丰喬,余佳慧 | |
dc.subject.keyword | 表皮生長因子受體,酪氨酸激?抑制劑,溶素,粒線體,非小型肺癌細胞,黃綠青黴素, | zh_TW |
dc.subject.keyword | EGFR,TKI,MMP7,mitochondria,NSCLC,citreoviridin, | en |
dc.relation.page | 68 | |
dc.identifier.doi | 10.6342/NTU201603199 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2016-08-18 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
顯示於系所單位: | 生物化學暨分子生物學科研究所 |
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