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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 康照洲 | |
dc.contributor.author | Yu-Hsuan Yang | en |
dc.contributor.author | 楊于萱 | zh_TW |
dc.date.accessioned | 2021-06-16T17:41:22Z | - |
dc.date.available | 2017-09-19 | |
dc.date.copyright | 2012-09-19 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-08-14 | |
dc.identifier.citation | 參考文獻 (References)
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64335 | - |
dc.description.abstract | 多環芳香烴受體 (Aryl hydrocarbon receptor, AhR) 是一配體活化之轉錄因子,當接觸到環境汙染物多環芳香烴 (polycyclic aromatic hydrocarbon, PAH) 時多環芳香烴受體 (Aryl hydrocarbon receptor, AhR) 會被活化並啟動下游基因表現。細胞上皮-間質轉換 (epithelial - mesenchymal transition, EMT) 是指在生理上胚胎發育及癌症發展過程中,細胞失去上皮細胞緊密結合型態的過程。EMT不僅促進胚胎發育過程中型態改變,在癌症中更促使癌細胞侵襲及轉移。過去文獻報導,多環芳香烴苯芘 (benzo[a]pyrene, B[a]P) 會藉由活化AhR,造成細胞中許多EMT指標在mRNA的表現呈現促進EMT現象。此外,亦有文獻指出,AhR在未與任何PAH結合活化的情形下,與調節細胞骨架重組、細胞型態及爬行能力有關。然而,AhR在未活化的狀態下與EMT之間的關係目前還是未知。因此,本研究目的在探討AhR於EMT機轉當中所扮演的角色。首先,從A549、H1299及CL1-5、CL1-0兩組肺癌細胞株發現,當細胞AhR表現量多時細胞侵襲能力小,而AhR表現量少則細胞侵襲能力大,後續我們選取AhR含量較少之H1299細胞做AhR大量表現載體 (AhR overexpressing vector) 的暫時性轉染,發現AhR大量表現之H1299其細胞型態呈現較為狹長且侵襲能力下降。利用核質分離及免疫螢光染色發現大量表現之AhR多分布於細胞質中,而處理AhR配體苯芘 (Benzo[a]pyrene) 後AhR進核並可誘導下游基因CYP1B1的產生。進一步探討作用機轉其對EMT指標之影響,發現間質指標 (mesenchtmal marker)─vimentin在AhR大量表現之劑量及時間效應實驗上蛋白質表現量有顯著下降,但mRNA表現量不受影響,此外,vimentin上游GTPases家族中之Rac1亦只在蛋白質表現量有下降現象,顯示AhR可能是透過轉譯後修飾對蛋白質進行調節作用。然而,Rac1抑制劑NSC23766處理無法回復由AhR大量表現所造成之vimentin抑制,但仍可看到磷酸化型式之vimentin有上升現象,可知AhR大量表現所引發的vimentin抑制並非經由Rac1所調控。另一方面,處理MG132後可回復AhR大量表現造成之Rac1及vimentin抑制,進而利用免疫沉澱法發現當AhR大量表現時AhR與Rac1、Ubiquitin、vimentin及phospho-vimentin之間交互作用皆有增之加現象。 | zh_TW |
dc.description.abstract | Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor. It will translocate into nucleus and may directly linked to transcriptional activation of target genes in response to ligands, polycyclic aromatic hydrocarbon (PAH). Epithelial - mesenchymal transition (EMT) is a process in which epithelial cells lose its intercellular adhesion during critical phases such as embryonic development and tumor progression. Previous studies have shown that EMT will be induced by ligand-activated AhR through activating a transcription factor of EMT. However, in our study, the non-activated AhR could decrease EMT in H1299 cell, and the detailed mechanism is still unknown. In this study, we found that the level of AhR expression in different lung cancer cells was correlated with their invasive potential. H1299 cell, which expressed AhR in low basal level, showed a high expression level in vimentin, an EMT marker, and showed a higher invasive ability (compared with A549, lung epithelial cell with high-level AhR expression and lower invasive ability). When AhR overexpression in H1299, not only the expression of vimentin was reduced, but the invasive cell was suppressed. Although the vimentin protein level was changed in AhR overexpressed cell, whereas the mRNA level was remained unaffected. We also found the overexpressed AhR protein was stayed in cytosol, and without transcriptional activity until the stimulation of B[a]P, suggested the anti-EMT function of AhR was independent of their transactivational activity. Moreover, non-activated AhR reduced the protein expression level of GTPase exchange factor (GEF), Rac1, and without change in their mRNA level. However, treatment of Rac1 inhibitor NSC23766 did not reverse the decrease in vimentin, and the phospho- vimentin still increased, suggested that overexpressed-AhR regulate vimentin through Rac1-independent pathway. Moreover, we found that the protein-protein interaction between AhR and Rac1, Ubiquitin, vimentin, phospho-vimentin was increased in AhR-overexpressed H1299 cell. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T17:41:22Z (GMT). No. of bitstreams: 1 ntu-101-R99447005-1.pdf: 2597546 bytes, checksum: 1ba28ea8806f255a0452afd2e4d86fae (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 目錄 (Contents)
口試委員會審定書 謝誌 縮寫表(Abbreviations) ……………………………….………………………....…...v 圖表目錄(Figures and Tables) ………………………………...……………….…......vi 中文摘要………………………………………….….………………………….…....vii 英文摘要………………………………………………………………………….…ix 第一章 緒論 ( Introduction ) 1.1多環芳香烴受體 (Aryl hydrocarbon receptor, AhR)在細胞中的角色..........……2 1.2上皮間質轉移 (Epithelial-Mesenchymal Transition, EMT)作用與EMT markers…………...... ……….…………………………………………………….4 1.3多環芳香烴受體 (AhR) 與EMT之調控…………………….………...................6 1.4細胞骨架的介紹......................................................................................................7 1.5細胞骨架vimentin與vimentin的調控…….……………………………..………7 1.6多環芳香烴受體 (AhR)對細胞骨架、型態的影響……………………………..9 1.7研究動機……………………………………………..…………………………..10 第二章 實驗材料與方法 ( Materials and Methods ) 2.1 實驗材料…..…………….………………………………………….….……......13 2.1.1細胞株 (Cell lines)…..………...……….…………………………….….…......13 2.1.2藥品與試劑 (Chemicals and Reagents)………….………………….…..…….13 2.1.3抗體 (Antibodies)……………….…………..………………………….….......14 2.1.4質體 (Plasmids)…….……….…………………………………….….…..........15 2.2 實驗方法…………………………………………………………………….…..15 2.2.1細胞培養 (Cell culture)………………………………………………..………15 2.2.2 細胞總蛋白質液收集 (Cell lysate collection)…..…………………................16 2.2.3 西方墨點法 (Western blot analysis)................................................................16 2.2.4 免疫沉澱法 (Immunoprecipitation)………….………………………….......17 2.2.5細胞RNA萃取 (RNA extraction)……………………………………………17 2.2.6反轉錄聚合酶鏈鎖反應 (Reverse Transcription Polymerase Chain Reaction, RT-PCR).……………..……….………....…...................................................17 2.2.7質體轉染 (Plasmid transfection)……………..……..……..…………………..18 2.2.8細胞核質分離 (Nuclear and cytoplasmic fraction)……..…………..…………18 2.2.9免疫螢光染色 (immunofluorescence staining)………………………………..19 2.2.10細胞侵襲試驗 (Cell invasion assay)………………………………………....19 2.2.11統計分析(Statistic analysis)………………………………………….……….20 第三章 實驗結果 ( Results ) 3.1肺癌細胞株A549、H1299、CL1-5、CL1-0多環芳香烴受體 (AhR)表現量與 其細胞侵襲能力的關係…....................................................................................22 3.2未活化之多環芳香烴受體 (AhR)大部分存在於細胞質……………...……….23 3.3多環芳香烴受體 (AhR)大量表現抑制EMT markers當中vimentin蛋白質表 現但不影響其mRNA表現.….............................................................................24 3.4多環芳香烴受體 (AhR)大量表現抑制Rac1蛋白質表現但不影響其mRNA 表現……………………………………………………………………...……….25 3.5 NSC23766無法回復大量表現之AhR所抑制之vimentin蛋白表現量…...…26 3.6 MG132回復了大量表現之AhR所抑制之vimentin及Rac1蛋白質表現……27 3.7多環芳香烴受體 (AhR)大量表現增進H1299細胞AhR與Rac1及Ubiquitin 之間的交互作用…………………………………….………………….……....27 3.8多環芳香烴受體 (AhR)大量表現增進H1299細胞AhR與vimentin之間的交互作....………..………………………………………………………………………28 3.9多環芳香烴受體 (AhR)靜默增進了A549細胞的侵襲能力………………..…29 第四章 討論 ( Discussion ) 4.1細胞中多環芳香烴受體 (AhR) 表現量對癌細胞發展影響之探討……….…31 4.2大量表現之多環芳香烴受體 (AhR) 於核內外分布之探討……………….…34 4.3多環芳香烴受體 (AhR) 對EMT markers影響之探討…………………….…36 4.4細胞骨架vimentin的調控─磷酸化之機制探討………………………….…...37 4.5多環芳香烴受體 (AhR) 與Rac1、vimentin、p-vimentin之間交互作用之探討………………………………………….……………………….……………38 第五章 結論 (Conclusion) ...……...........................................................................41 參考文獻 (References) ………..................................................................................43 圖表集 (Figures and Tables) ......................................................................................55 | |
dc.language.iso | zh-TW | |
dc.title | 在肺癌細胞株H1299探討EMT指標vimentin之調控機制:多環芳香烴受體之角色探討 | zh_TW |
dc.title | Studies on the Mechanism of Regulation in EMT marker Vimentin in H1299:The Role of Aryl Hydrocarbon receptor | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 顏茂雄,鄭幼文 | |
dc.subject.keyword | 多環芳香烴受體,上皮間質轉移,vimentin,Rac1, | zh_TW |
dc.subject.keyword | Aryl hydrocarbon receptor (AhR),Epithelial mesenchymal transition (EMT),vimentin,Rac1, | en |
dc.relation.page | 72 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-08-15 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 毒理學研究所 | zh_TW |
顯示於系所單位: | 毒理學研究所 |
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