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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 阮雪芬(Hsueh-Fen Juan) | |
| dc.contributor.author | Nai-Ning Chen | en |
| dc.contributor.author | 陳乃寧 | zh_TW |
| dc.date.accessioned | 2021-06-17T00:10:54Z | - |
| dc.date.available | 2017-07-18 | |
| dc.date.copyright | 2012-07-18 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-07-13 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65745 | - |
| dc.description.abstract | ATP 合成酶在所有生物體中皆存在，且通常位於真核細胞粒線體的內膜上。我們先前的研究發現，相較於正常細胞，ATP合成酶在乳癌組織中表現量較高，且在腫瘤細胞表面上出現 (Journal of Proteome Research, 2008)。在此我們發現citreoviridin在MCF-7細胞中能顯著地抑制增生，原因可能為其具有促進細胞週期停滯之能力。為了能更清楚的闡述citreoviridin的機制，我們設計了一個結合二維電泳與基質輔助雷射脫附游離質譜儀的蛋白質體學實驗。藉由比較加入citreoviridin與對照組的蛋白質體，我們發現表現量出現明顯差異的蛋白質主要與蛋白質的摺疊有關。累積大量的未折疊蛋白在內質網的內膜上會活化未折疊蛋白質反應並造成細胞週期停滯在G0/G1期。我們證明citreoviridin可使細胞週期停滯在G0/G1期是藉由引發未折疊蛋白質反應，造成eIF2α的磷酸化並抑制轉譯，最後阻礙一般蛋白質合成，當中包括細胞週期調節因子cyclin D1和retinoblastoma蛋白。最後的結果證明citreoviridin這個ATP合成酶抑制劑是一具有潛力的乳癌治療藥物。 | zh_TW |
| dc.description.abstract | ATP synthase presents in all organisms and usually located on the membrane of mitochondria of eukaryotic cells. Our previous study showed that ATP synthase was upregulated in breast cancer tissues and could be expressed on tumor cell surface more than on normal cell surface (Journal of Proteome Research, 2008). Here, we found that citreoviridin displayed significant anti-proliferative activity in MCF-7 cells, which may be attributed to its induction of cell cycle arrest. To further elucidate the mechanism of citreoviridin, we performed a proteomic study combining two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. By comparing citreoviridin-treated and control proteome profiles of MCF-7 cells, we found the major function of these differential expressed proteins was related to protein folding. Accumulation of unfolded proteins in the lumen of the ER could activate the unfolding protein response (UPR), which could induce cell cycle arrest at G0/G1 phase. We demonstrated that citreoviridin could induce cell cycle arrest at G0/G1 phase through triggering of UPR, the phosphorylation of eIF2α and induction of translational inhibition, thereby blocking general protein synthesis including the cell cycle regulator cyclin D1 and retinoblastoma protein. Our results showed that ATP synthase inhibitor citreoviridin could be a potential drug for breast cancer therapy. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T00:10:54Z (GMT). No. of bitstreams: 1 ntu-101-R98b43014-1.pdf: 3231398 bytes, checksum: 586a3e015aaf74fd548e6232def56a30 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | Contents
口試委員會審定書 I 誌謝 II 中文摘要 IV Abstract V Contents VI List of Figures X List of Table XII Chapter 1 Introduction 1 1.1 Breast cancer 1 1.2 Targeting therapy 1 1.3 ATP synthase 2 1.4 ATP synthase inhibitor 4 1.5 Endoplasmic reticulum 4 1.6 Unfolding protein response 5 1.7 The role of BiP under ER stress 6 1.8 ER stress signaling 6 Chapter 2 Materials and Methods 8 2.1 Cell culture 8 2.2 Immunofluorescence 8 2.3 RTCA system 9 2.4 Colony formation assay 9 2.4.1 anchorage-dependent 9 2.4.2 anchorage-independent 10 2.5 Cell cycle analysis 11 2.6 Protein extraction 11 2.7 Western blot 12 2.8 Two dimensional electrophoresis (2DE) 13 2.9 In gel digestion 14 2.10 Protein identification 14 2.11 Small interfering RNAs and transfection 15 Chapter 3 Results 16 3.1 ATP synthase is present on the surface of MCF-7 cells 16 3.2 Citreoviridin inhibits the proliferation of MCF-7 breast cancer cells but not MCF-10A epithelial cells. 17 3.3 Citreoviridin induced MCF-7 cell cycle arrest at G0/G1 phase. 18 3.4 Citreoviridin decreased the expression of cyclin D1, Cdk4, and P-Rb. 18 3.5 Citreoviridin increased the expression of cyclin-dependent kinase inhibitor p21. 19 3.6 Identified proteins after citreoviridin treatment in MCF-7 cells 20 3.7 Citreoviridin induced unfolding protein response which is confirmed by western blot 21 3.8 Knockdown PERK decrease the phosphorylation of eIF2α 22 Chapter 4 Discussion 23 Chapter 5 Future works 27 Reference 28 Figures 38 Table 59 Appendix 60 Conference Proceeding：The 26th Joint Annual Conference of Biomedical Sciences, Taipei, Taiwan, March 19-20, 2011 61 國立台灣大學分子與細胞生物學研究所99學年度壁報競賽 62 | |
| dc.language.iso | en | |
| dc.subject | ATP合成酶 | zh_TW |
| dc.subject | 乳癌 | zh_TW |
| dc.subject | citreoviridin | zh_TW |
| dc.subject | 抑制生長 | zh_TW |
| dc.subject | breast cancer | en |
| dc.subject | ATP synthase | en |
| dc.subject | citreoviridin | en |
| dc.subject | anti-proliferative | en |
| dc.title | 探討ATP合成酶抑制劑citreoviridin抑制乳癌生長作用機制 | zh_TW |
| dc.title | Elucidating the molecular mechanism of ATP synthase inhibitor citreoviridin on anti-proliferative activity of breast cancer cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 黃宣誠(Hsuan-Cheng Huang),陳水田(Shui-Tein Chen),李岳倫(Yueh-Luen Lee),徐駿森(Chun-Hua Hsu) | |
| dc.subject.keyword | ATP合成酶,乳癌,citreoviridin,抑制生長, | zh_TW |
| dc.subject.keyword | ATP synthase,citreoviridin,breast cancer,anti-proliferative, | en |
| dc.relation.page | 62 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-07-13 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
| 顯示於系所單位： | 分子與細胞生物學研究所 | |
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