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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 楊雅倩(Ya-Chien Yang) | |
dc.contributor.author | Hoi-Yan Lio | en |
dc.contributor.author | 廖凱欣 | zh_TW |
dc.date.accessioned | 2021-05-20T21:15:21Z | - |
dc.date.available | 2014-03-03 | |
dc.date.available | 2021-05-20T21:15:21Z | - |
dc.date.copyright | 2011-03-03 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-02-08 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/10265 | - |
dc.description.abstract | 根據台灣行政院衛生署2008年死因統計資料,大腸直腸癌在男性或女性中都是排名第三位的癌症死因。之前本研究室針對大腸直腸癌腫瘤檢體進行第四號染色體之微衛星標記發生失異合性(loss of heterozygosity, LOH)的分析,發現4q25-4q28.3中有3個發生頻率較高(23.1%-28.0%)的刪除區域。而在其他癌症亦被報導第四號染色體之長臂(q arm)有發生刪除的現象,進而推論第四號染色體可能存在抑癌基因。在本研究室發現的一個頻率較高的刪除區域(4q28.3),存在一細胞吸附分子Protocadherin 10 (PCDH10)基因。目前知道PCDH10有兩種RNA產物,分別為PCDH10 variant 1 (PCDH10 V1)和PCDH10 variant 2 (PCDH10 V2)。近來的研究發現在其他癌症當中,PCDH10可能扮演著抑癌基因的角色。除了染色體的刪除,本研究室之前針對PCDH10於大腸直腸癌中基因後生遺傳修飾的研究,發現PCDH10基因啟動子(promoter)有過度甲基化的現象。再者,其mRNA在大腸直腸癌的腫瘤組織之表現,明顯地比其成對之正常黏膜組織較低。之後亦針對PCDH10進行了功能性的探討,發現當PCDH10在大腸直腸癌細胞株中再度表現後,可以抑制癌細胞侵犯以及群落形成,進一步顯示PCDH10可能為抑癌基因。本論文利用重新挑選的PCDH10 V1和PCDH10 V2之穩定表現細胞株,先進行細胞增生的實驗,發現當PCDH10 V1於大腸直腸癌細胞再表現時,會抑制細胞的生長,但再表現PCDH10 V2則觀察不到同樣的現象。之後再進行促進細胞凋亡的實驗,無論是PCDH10 V1或是PCDH10 V2皆可促進細胞凋亡。除此之外,利用藥物camptothecin處理PCDH10 V1或PCDH10 V2再表現之細胞株,結果顯示當PCDH10存在時會增加癌細胞對藥物的感受性。另外,本論文亦設計四個分佈在PCDH10基因5端和3端的微衛星標記,針對大腸直腸癌腫瘤探討PCDH10發生對偶基因缺失(allelic deletion)的情形。於191個大腸直腸癌腫瘤檢體中,有57個(29.8%)發生PCDH10對偶基因的缺失,同時,此基因變異與大腸直腸癌後期的轉移相關,且病人之存活率亦較差。由於研究室之前曾針對PCDH10進行基因後生遺傳修飾的探討,故利用其結果,配合對偶基因缺失與否,進行病人存活分析,而當同時探討此兩種基因變化時,其與病人的存活率並沒有顯著的相關性。最後,本論文亦利用DNA套數檢測(copy number assay)以研究大腸直腸癌腫瘤中PCDH10基因套數的變異,並與LOH研究的結果相比較,結果顯示此二方法的結果並不完全符合。綜合以上結果,PCDH10的再表現可以促進大腸直腸癌細胞之凋亡,同時此基因在大腸直腸癌腫瘤中有高比例之腫瘤發生對偶基因缺失的現象,皆進一步支持PCDH10在大腸直腸癌化過程中具有抑癌的功能。 | zh_TW |
dc.description.provenance | Made available in DSpace on 2021-05-20T21:15:21Z (GMT). No. of bitstreams: 1 ntu-100-R97424013-1.pdf: 2626001 bytes, checksum: 204239c9cb7d488499749adf0ff93659 (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | Acknowledgement i
摘要 ii Abstract iv Content vi Abbreviation viii Figure content ix Table content xi 1. Introduction 1 1.1 Colon and rectum 1 1.2 Colorectal cancer 2 1.2.1 Two major pathways in colorectal carcinogensis 3 1.2.2 Epigenetic pathway in colorectal carcinogenesis 4 1.3 Protocadherin 10 (PCDH10) 5 1.3.1 Recent studies of PCDH10 6 1.3.2 PCDH10 and apoptosis 8 1.3.3 Deletion of chromosome 4q28 and cancer 9 1.3.4 Studies of PCDH10 at our lab 9 2. Specific aims 11 3. Materials and methods 12 3.1 Study of cell biological functions of PCDH10 12 3.1.1 Cell culture 12 3.1.2 Vector construction 12 3.1.3 Cell transfection and stable clone selection 13 3.1.4 Western blotting 14 3.1.5 Cell proliferation assay 14 3.1.6 Camptothecin treatment 15 3.1.7 Flow cytometry analysis for apoptosis 15 3.1.8 Study of epithelial-to-mesenchymal transition 16 3.2 Study of allelic deletion of PCDH10 17 3.2.1 Patients 17 3.2.2 DNA extraction 18 3.2.3 Loss of heterozygosity study 18 3.2.4 Automated fluorescence-based PCR assay 19 3.2.5 Copy number assay 20 3.3 Statistical analysis 20 4. Results 22 4.1 Cell biological functions of PCDH10 22 4.1.1 Selection of PCDH10 variant 1 and PCDH10 variant 2 single stable clones 22 4.1.2 Apoptosis induced by PCDH10 23 4.1.3 Regulation of epithelial-to-mesenchymal transition by PCDH10 24 4.2 Allelic deletion of PCDH10 25 4.2.1 Loss of heterozygosity of PCDH10 25 4.2.2 Copy number variation of PCDH10 30 5. Discussion 32 Figures 39 Tables 56 References 68 Appendix 72 | |
dc.language.iso | en | |
dc.title | PCDH10於大腸直腸癌促進細胞凋亡及其基因刪除之探討 | zh_TW |
dc.title | Study of proapoptotic activity and allelic deletion of PCDH10 in colorectal cancer | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林淑萍(Shwu-Bin Lin),俞松良(Sung-liang Yu),蔡明宏(Ming-Hong Tsai) | |
dc.subject.keyword | 大腸直腸癌,失異合性,PCDH10,細胞凋亡,對偶基因缺失, | zh_TW |
dc.subject.keyword | Colorectal cancer,Loss of heterozygosity,PCDH10,Proapoptotic activity,Allelic deletion, | en |
dc.relation.page | 75 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2011-02-08 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
顯示於系所單位: | 醫學檢驗暨生物技術學系 |
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