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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳燕惠(Yen-Hui Chen) | |
| dc.contributor.author | Ming-Hung Hou | en |
| dc.contributor.author | 侯明宏 | zh_TW |
| dc.date.accessioned | 2021-06-15T16:10:16Z | - |
| dc.date.available | 2020-09-24 | |
| dc.date.copyright | 2015-09-24 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-18 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/52249 | - |
| dc.description.abstract | 上皮間葉轉化 (epithelial mesenchymal transition，EMT) 對於癌細胞產生抗藥性及造成較差的預後有相當程度影響力。文獻指出，EMT過程的許多轉錄因子扮演重要的角色，如CDH1/2, ZEB1/2, Twist, Snail 1/2等。先前我們實驗室的研究發現在具 doxorubicin 抗藥性的MCF-7/ADR細胞株中表現出大量的Slug (Snail2) 蛋白質，而野生型MCF-7 (MCF-7/WT)則未偵測到。所以本研究主要探討外加Slug 對MCF-7/WT 細胞的影響。 首先利用反轉錄聚合酶連鎖反應技術，從 MCF-7/ADR 細胞中純化出Slug基因，再利用重組質體建構技術建構出帶有Slug 基因的質體，接著將質體利用轉染技術送入MCF-7/WT 細胞中瞬時大量表現，並以反轉錄聚合酶連鎖反應及西方墨點法方法觀察E-cadherin、ERα及抗氧化基因如Nrf2與HO-1的表現。 實驗結果顯示，大量表現Slug蛋白質的MCF-7細胞比對照組細胞具有更高的遷移能力，而上皮細胞標記因子，如E-cadherin、ERα的表現降低，並且具有較明顯的抗氧化基因如Nrf2、HO-1的表現，且有關細胞凋亡分子Bax、Bad亦受到Slug抑制，此結果顯示Slug的表現可能使細胞表現更多間質細胞特性的表徵。另外，細胞中加入不同濃度的doxorubicin，則大量表現Slug的細胞，其cleaved PARP的表現降低。文獻中指出GSK3β可調控下游Slug蛋白質的降解，所以本實驗利用GSK3β抑制劑 (LiCl) 來抑制GSK3β蛋白質，結果顯示LiCl與瞬時表現的Slug共同的存在下，能更快速促進上皮細胞標記因子，如E-cadherin、ERα的減少及促進抗氧化基因的表現。綜合所有結果顯示，Slug在誘導MCF-7/WT走向EMT中佔了重要的角色，未來Slug蛋白質在癌症治療上可以做為一個有效的標的。 | zh_TW |
| dc.description.abstract | Epithelial mesenchymal transition (EMT) is important for cancer cells progression and poor prognosis. Studies show that many transcription factors play important roles in EMT formation such as CDH1/2, ZEB1/2, Twist, Snail 1/2. Previous study from our labatory found that the doxorubicin-resistant breast cancer cell line MCF-7/ADR expressed high level of Slug (Snail2) protein expression, compared to the doxorubicin-sensitive breast cancer cell line MCF-7/WT. The aim of this thesis was to study the effect of Slug in MCF-7/WT cells. The full-length coding sequence of Slug was amplified from MCF-7/ADR using RT-PCR. Then the cloning technique was applied to construct the recombinant plasmid pSlug. The pSlug was transiently transfected into MCF-7/WT cells and the expression of E-cadherin, ERα and antioxidant genes Nrf2 and HO-1 were detected. Data revealed that in the Slug-overexpressed MCF-7/WT cells, the migration ability increased. The epithelial marker E-cadherin and ERα were downregulated and the antioxidant genes Nrf2 and HO-1 were upregulated, compared to control MCF-7/WT. The expression of apoptotic factors Bax and Bad was also downregulated in the Slug-overexpressed MCF-7/WT. On the other hand, the level of cleaved PARP protein decreased in the MCF-7/WT which transiently overexpressed Slug, accompanied with doxorubicin treatment. Since the Slug stability was regulated by GSK3β, the GSK3β inhibitor (LiCl) slightly stabilized Slug and accelerated downregulation of the expression of E-cadherin and ERα and upregulated the antioxidant genes Nrf2 and HO-1 in MCF-7/WT cells. Taken together, Slug may play an important role in EMT development in MCF-7/WT, and could be a crucial factor in cancer treatment in the future. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T16:10:16Z (GMT). No. of bitstreams: 1 ntu-104-R01423021-1.pdf: 2471692 bytes, checksum: fa2aac3b0cd9fc9f9cb609d4a412299f (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 中文摘要 i Abstract iii 目錄 v 圖表目錄 viii 縮寫對照表 ix 第一章、緒論 1 1.1乳癌與MCF-7 1 1.2 上皮間葉轉化 (Epithelial-mesenchymal transition) 1 1.3 轉錄因子在上皮間葉轉化的重要性 2 1.4 調控上皮間葉轉化關鍵轉錄因子的主要路徑 4 1.5 Slug正常生理功能及在癌症中可能造成之影響 6 1.6 GSK3β生理功能與Snail家族交互作用 7 1.7 ERα與上皮間葉轉化的關聯性 8 1.8 Nrf2在癌症與上皮間葉轉化扮演的角色 9 1.9 Nrf2及ERα在上皮間葉轉化中關聯性 11 1.10 研究目的 11 第二章、材料與研究方法 12 2.1 實驗儀器 12 2.2實驗材料 13 2.3 培養液、培養基與緩衝液之配製 14 2.4 實驗方法 16 一、 培養基之製備 16 二、 細胞株培養 16 三、 質體建構 (Construction of plasmid ) 16 四、 小量質體製備 17 五、 大量質體製備 18 六、 轉染試驗 (Transfection ) 18 七、 細胞毒殺試驗 (MTT assay) 18 八、 傷口癒合試驗 (wound healing assay) 18 九、 反轉錄-聚合酶連鎖反應法 (Reverse Transcription-PCR) 19 十、 西方點墨法 (Western blot) 20 十一、 統計檢定 22 第三章、實驗結果 23 1.製備並確認帶有Slug基因的質體 23 2.Slug表現促進MCF-7細胞的遷移能力 23 3.Slug表現使MCF-7細胞降低上皮細胞標記因子表現並增加抗氧化基因表現 24 4.Slug表現降低doxorubicin引起的細胞凋亡分子PARP的表現 24 5.GSK3β抑制劑 (LiCl) 加速Slug引起的基因表現改變 25 第四章、討論 27 第五章、結論 31 第六章、圖表 32 第七章、參考文獻 49 | |
| dc.language.iso | zh-TW | |
| dc.subject | MCF-7/WT | zh_TW |
| dc.subject | Slug | zh_TW |
| dc.subject | 上皮間葉轉化 | zh_TW |
| dc.subject | E-cadherin | zh_TW |
| dc.subject | ERα | zh_TW |
| dc.subject | GSK 3β | zh_TW |
| dc.subject | Nrf2 | zh_TW |
| dc.subject | HO-1 | zh_TW |
| dc.subject | ERα | en |
| dc.subject | HO-1 | en |
| dc.subject | Nrf2 | en |
| dc.subject | Slug | en |
| dc.subject | epithelial mesenchymal transition | en |
| dc.subject | E-cadherin | en |
| dc.subject | GSK 3β | en |
| dc.subject | MCF-7/WT | en |
| dc.title | Slug對乳癌細胞株MCF-7的影響 | zh_TW |
| dc.title | The effect of Slug in the MCF-7 breast cancer cell line | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 許麗卿,楊家榮,張國友,駱雨利 | |
| dc.subject.keyword | Slug,上皮間葉轉化,E-cadherin,ERα,GSK 3β,Nrf2,HO-1,MCF-7/WT, | zh_TW |
| dc.subject.keyword | Slug,epithelial mesenchymal transition,E-cadherin,ERα,GSK 3β,Nrf2,HO-1,MCF-7/WT, | en |
| dc.relation.page | 60 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-08-19 | |
| dc.contributor.author-college | 藥學專業學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| 顯示於系所單位： | 藥學系 | |
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