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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81078完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 華國泰(Kuo-Tai Hua) | |
| dc.contributor.author | Ya-Ting Qian | en |
| dc.contributor.author | 錢雅婷 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:29:27Z | - |
| dc.date.available | 2026-09-08 | |
| dc.date.available | 2022-11-24T03:29:27Z | - |
| dc.date.copyright | 2021-10-01 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-09-10 | |
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Mol Cell, 2012. 48(1): 28-38. 50.Sinha, S., et al., Alterations in candidate genes PHF2, FANCC, PTCH1 and XPA at chromosomal 9q22.3 region: pathological significance in early- and late-onset breast carcinoma. Mol Cancer, 2008. 7: 84. 51.Sun, L.L., et al., Overexpression of Jumonji AT-rich interactive domain 1B and PHD finger protein 2 is involved in the progression of esophageal squamous cell carcinoma. Acta Histochem, 2013. 115(1): 56-62. 52.Zhang, l., et al., Significance of PHF2 expression in breast cancer. J Clin Exp Pathol, 2016. 32(1): 4-8. 53.Ghosh, A., et al., Inactivation of 9q22.3 tumor suppressor genes predict outcome for patients with head and neck squamous cell carcinoma. Anticancer Res, 2013. 33(3): 1215-1220 54.Lee, K.H., et al., PHF2 histone demethylase acts as a tumor suppressor in association with p53 in cancer. Oncogene, 2015. 34(22): 2897-909 55.Lee, C., et al., Implication of PHF2 Expression in Clear Cell Renal Cell Carcinoma. 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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81078 | - |
| dc.description.abstract | "腎細胞癌是泌尿系統中惡性度較高的腫瘤，佔所有惡性腫瘤的2%~3%，近年來腎細胞癌的發病率年均增長約2%。在病理上腎細胞癌分為四類，其中腎透明細胞癌占85%，且相較於其他類型的腎細胞癌預後更差。植物同源結構域（plant homeodomain, PHD結構域）是真核生物中一種進化保守的鋅指結構域,多種調控基因轉錄、細胞週期、凋亡的蛋白質含有PHD結構域，通常參與蛋白質之間的相互作用，特別是對核小體組蛋白進行甲基化、乙醯化、磷酸化等修飾。過去多個研究發現，Plant homeodomain finger 2（PHF2）在頭頸部腫瘤、結腸癌、胃癌等多種惡性腫瘤中表現量低，提示PHF2對腫瘤發生發展起負向調控作用，也許在癌症中扮演腫瘤抑制的角色。因此在本研究中，我們試圖探討PHF2在腎細胞癌中的角色，以評估其作為新穎腎細胞癌藥物或生物標誌的可能性。首先借由癌症基因組圖譜（The Cancer Genome Atlas，TCGA）發現，PHF2蛋白在腎細胞癌病人中低表現，且表現量較低的病人存活率較差，提示其可作為腎細胞癌預後標的分子。目前透過選擇初代腎透明細胞癌細胞786-O、轉移腎細胞癌細胞CAKI-1和未分類的A498細胞，以及合適的PHF2片段，進行多個體外實驗，發現抑制PHF2的表現量，使細胞生長速度、短/長期集落形成能力，轉移以及侵襲能力上升，而過表現PHF2則下降，與各細胞特性相符。在動物實驗中，我們以原位注射方式，給予NSG小鼠腎透明細胞癌細胞，發現控制組小鼠腫瘤出現兩側腎臟轉移和肺轉移，而過表現PHF2組別的小鼠不見明顯腫瘤。為了進一步釐清PHF2可能調控的基因，我們使用基因集富集分析（ Gene Set Enrichment Analysis，GSEA），找到多個相關基因，並進行qPCR分析，但未能找到在三株細胞中，結果一致的基因。但根據目前所得到的數據，我們還是可以確定PHF2在腎透明細胞癌中扮演了腫瘤抑制基因的角色，但其調控機制及下游調控因子還需更多的研究，以便為腎細胞癌患者在預後、治療藥物及生物標誌等方面提供新思路。" | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:29:27Z (GMT). No. of bitstreams: 1 U0001-2008202112440700.pdf: 3950109 bytes, checksum: 447ea6e59a83b13cbf15f63a3e313f63 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "誌謝………………………………………………………………………………………i 縮寫表…………………………………………………………………………………ii 中文摘要……………………………………………………………………………iii 英文摘要………………………………………………………………………………v 第一章 介紹……………………………………………………………………………1 1.1腎癌…………………………………………………………………………………2 1.2腎細胞癌……………………………………………………………………………2 1.3腎透明細胞癌………………………………………………………………………5 1.4腎透明細胞癌細胞株………………………………………………………………6 1.4.1 786-O細胞株………………………………………………………………………6 1.4.2 CAKI-1細胞株……………………………………………………………………7 1.4.3 A498細胞株………………………………………………………………………7 1.5植物同源異域指2（Plant Homeodomain Finger 2, PHF2）………………………7 1.5.1離胺酸特異性組蛋白脫甲基酶（Lysine-specific histone demethylase, KDM）…7 1.5.2 PHF2的作用………………………………………………………………………9 1.5.3在人類癌症中PHF2的角色……………………………………………………10 1.6研究目的……………………………………………………………………………11 第二章 材料與方法…………………………………………………………………12 2.1細胞株、細胞培養及繼代……………………………………………………… 13 2.2抗體，試劑與材料…………………………………………………………………14 2.3 pWPI-PHF2製備與轉染（transfection）………………………………………14 2.4慢病毒製備與轉染………………………………………………………………15 2.5蛋白質含量分析與核質分離分析………………………………………………15 2.6西方墨點法（western blot）………………………………………………………16 2.7定量即時聚合酶鏈鎖反應（Quantitative real time polymerase chain reaction, q-PCR）與微陣列（microarray）實驗…………………………………………………17 2.8細胞增生（cell proliferation）與集落形成（colony formation）實驗…………19 2.9細胞轉移（migration）與侵襲（invasion）實驗………………………………19 2.10細胞挽救實驗（Cellular rescue assay）………………………………………20 2.11體內原位癌腫瘤模型建立………………………………………………………21 2.12基因集富集分析（ Gene Set Enrichment Analysis，GSEA）分析………………21 2.13統計分析…………………………………………………………………………21 第三章 結果…………………………………………………………………………22 3.1腎透明細胞癌與PHF2的表現相關…………………………………………23 3.2通過選擇合適的方法和片段改變野生型腎透明細胞癌細胞株中PHF2的表現.23 3.3在腎透明細胞癌細胞株中抑制或過表現PHF2會影響細胞的短期和長期增生.24 3.4 PHF2調控腎透明細胞癌細胞株的移行和侵襲能力……………………………25 3.5確認PHF2對於腎透明細胞癌細胞株功能的影響……………………………26 3.6在小鼠體內通過過表現PHF2建設原位癌模型………………………………27 3.7深入研究在腎透明細胞癌細胞株中調控PHF2所影響的下游因數…………28 第四章 討論…………………………………………………………………………30 圖與圖例………………………………………………………………………………38 參考文獻……………………………………………………………………………67" | |
| dc.language.iso | zh-TW | |
| dc.subject | 腫瘤抑制基因 | zh_TW |
| dc.subject | 腎透明細胞癌 | zh_TW |
| dc.subject | 腎臟癌 | zh_TW |
| dc.subject | 原位注射模型 | zh_TW |
| dc.subject | kidney | en |
| dc.subject | orthotopic | en |
| dc.subject | PHF2 | en |
| dc.subject | ccRCC | en |
| dc.title | PHF2在腎細胞癌中的角色 | zh_TW |
| dc.title | The Roles of Plant Homeodomain Finger 2 (PHF2) in Renal cell carcinoma | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 簡銘賢(Hsin-Tsai Liu),李維駿(Chih-Yang Tseng) | |
| dc.subject.keyword | 腎透明細胞癌,腎臟癌,原位注射模型,腫瘤抑制基因, | zh_TW |
| dc.subject.keyword | ccRCC,PHF2,kidney,orthotopic, | en |
| dc.relation.page | 73 | |
| dc.identifier.doi | 10.6342/NTU202102540 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-09-11 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 毒理學研究所 | zh_TW |
| dc.date.embargo-lift | 2026-09-08 | - |
| 顯示於系所單位： | 毒理學研究所 | |
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