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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 楊雅倩(Ya-Chien Yang) | |
dc.contributor.author | Yu-Xin Xiao | en |
dc.contributor.author | 蕭聿昕 | zh_TW |
dc.date.accessioned | 2021-06-17T01:32:22Z | - |
dc.date.available | 2022-09-12 | |
dc.date.copyright | 2017-09-12 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-08-03 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67441 | - |
dc.description.abstract | 大腸直腸癌於全世界及台灣均是癌症死亡原因的前三名,且在台灣大腸直腸癌已攀升為每年發生率最高之癌症。本實驗室先前的研究,於人類第三號染色體 3p25.3-p26.3 鑑定 Contactin 4 (CNTN4) 於大腸直腸癌可能扮演抑癌基因的角色。於 HCT116 細胞表現 CNTN4 可抑制細胞增生、固著依賴性及非固著依賴性胞落形成的能力,同時,在活體動物實驗則發現表現 CNTN4 可以抑制裸鼠皮下腫瘤的生成。目前 CNTN4 的功能尚未清楚,本論文分為三個部分探討:(一) 以血管新生為主題,探討 CNTN4 能否透過抑制血管新生,以減緩腫瘤之生成,結果顯示,於異種移植腫瘤之小鼠模式發現 CNTN4 可減少腫瘤的血管密度,而於體外細胞模型則發現 CNTN4 可抑制促血管新生因子 uPA 之表現。(二) 以 siRNA 策略降低 CNTN4 表現後,進行體外細胞增生能力分析,以驗證 CNTN4 的抑癌角色,結果顯示,抑制 CNTN4 表現可以恢復 HCT116 細胞之增生能力。(三) 為了進一步了解 CNTN4 於細胞外之功能,故建構分泌型 CNTN4 表現質體,以轉染方式送入大腸直腸癌細胞株 HCT116,使其表現分泌型 CNTN4,並進行體外細胞增生能力分析,結果顯示,含有分泌型 CNTN4 之條件培養液可抑制細胞增生之能力。綜合以上結果,CNTN4 可抑制 uPA 之表現,並降低腫瘤的血管密度,且細胞膜之 CNTN4 與分泌型 CNTN4 皆可抑制大腸直腸癌細胞株 HCT116 之增生能力,對 HCT116 細胞具有生長抑制的功能。 | zh_TW |
dc.description.abstract | Colorectal cancer (CRC) is one of the top three leading causes of cancer death in the world and Taiwan. Nowadays, CRC is the cancer with the highest annual incidence in Taiwan. In our previous study, we have identified Contactin 4 (CNTN4) as a novel tumor suppressor gene located at chromosome 3p25.3-p26.3 that is lost in CRC tumors at a high frequency. Ectopic expression of CNTN4 in HCT116 cells could reduce cell proliferation, anchorage-dependent and anchorage-independent colony formation in vitro. Furthermore, CNTN4 expression could inhibit the tumorigenesis of subcutaneous xenograft in nude mice. The function of CNTN4 is still not clear currently. In the study, there are three specific aims. First, we focused on tumor angiogenesis. We investigated whether CNTN4 could inhibit angiogenesis to suppress tumorigenesis. The results showed that CNTN4 could decrease the microvessel density in the xenograft tumor mouse model and inhibit the expression of uPA, which is one of the pro-angiogenic factors. In the second part, by using siRNA strategy, we knockdowned CNTN4 expression of HCT116 cells and performed in vitro cell proliferation assay. The results showed that inhibition of CNTN4 expression could restore cell proliferation and thus confirmed the tumor suppressor function of CNTN4. In the third part, to explore the function of CNTN4 cleaved and shed from cell surface, we constructed a secretory CNTN4-expressing plasmid, pSecTag2 Hygro B/sCNTN4, and then transiently transfected it into CRC cells, HCT116. By in vitro cell proliferation assay, we demonstrated that conditioned medium containing secretory CNTN4 could inhibit cell proliferation. Taken together, CNTN4 could inhibit the expression of uPA and decrease the microvessel density of xenograft tumors. Either membrane-anchored CNTN4 or secretory CNTN4 could inhibit cell proliferation of HCT116. Accordingly, CNTN4 displays growth inhibition function on CRC cells. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T01:32:22Z (GMT). No. of bitstreams: 1 ntu-106-R04424005-1.pdf: 11017192 bytes, checksum: f7188c91b8a7e7f83d61e4b48c9f8652 (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 致謝 i
摘要 ii 縮寫對照表 iv 圖目錄 ix 表目錄 x ㄧ、緒論 1 1. 大腸直腸癌 1 1.1 大腸直腸癌簡介 1 1.2 大腸直腸癌生成機制 2 1.2.1 染色體不穩定性 (Chromosomal instability, CIN) 2 1.2.2 微衛星不穩定性 (Microsatellite instability, MSI) 2 1.2.3 CpG 島甲基化表現型 3 1.3 大腸直腸癌分期 3 1.3.1 Dukes 分期系統 3 1.3.2 TNM 分期系統 4 1.3.3 AJCC/UICC 分期系統 5 2. Contactin 4 (CNTN4) 6 2.1. Contactin 家族簡介 6 2.2. Contactin 4 簡介 7 2.3. CNTN4 與結合蛋白 8 2.3.1 CNTN4 與 PTPRG 的結合 8 2.3.2 CNTN4 與 APP 的結合 9 2.4 CNTN4 與癌症相關研究 10 3. 血管新生 11 3.1 血管新生簡介 11 3.2 腫瘤血管新生 (Neoangiogenesis) 11 3.3 尿激酶型血纖維蛋白溶解酶原活化因子 (urokinase-type plasminogen 13 activator , uPA) 13 3.3.1 uPA 簡介 13 3.3.2 uPA 訊息傳遞機制 13 3.3.3 uPA 與癌症 14 4. 實驗室先前 CNTN4 相關研究 15 4.1 第三號染色體之失異合性檢測 15 4.2 CNTN4 抑癌功能鑑定 15 二、研究目標 16 三、材料與方法 18 1. 試劑、材料及抗體 18 2. 細胞培養 18 3. CNTN4 條件培養液製備和保存 19 4. 蛋白質的抽取及定量 19 5. 西方墨點法 19 6. RNA 萃取 20 7. 反轉錄合成互補 DNA 21 8. 即時定量聚合酶連鎖反應 21 9. 免疫組織化學染色 22 10. siCNTN4 knockdown 22 11. 建構分泌型 CNTN4 (secretory CNTN4 , sCNTN4) 表現質體 23 11.1 TA cloning 23 11.2 Restriction enzyme cloning 23 11.3 Site-directed mutagenesis 24 12. 細胞轉染及穩定表現分泌型 CNTN4 細胞株篩選 24 14. 細胞增生分析 25 15. 統計方法 25 四、研究結果 26 1. CNTN4 抑制 HCT116 細胞於裸鼠皮下腫瘤之血管新生 26 2. CNTN4 表現可降低促血管新生因子 uPA mRNA 表現程度 26 3. CNTN4 表現可降低促血管新生因子 uPA 蛋白表現程度 27 4. 以 siRNA 抑制 CNTN4 表現可提升 HCT116 細胞之增生能力 28 5. 建構分泌型 CNTN4 表現質體及挑選穩定表現分泌型 CNTN4 細胞株 28 6. 分泌型 CNTN4 使 HCT116 細胞之增生能力下降 29 五、討論 30 圖 36 表 45 參考文獻 48 附圖 58 | |
dc.language.iso | zh-TW | |
dc.title | 探討 Contactin 4對大腸直腸癌之促血管新生因子 uPA 的調控及表現分泌型 Contactin 4 蛋白 | zh_TW |
dc.title | Study of Contactin 4-modulated pro-angiogenic factor uPA expression in colorectal cancer and expression of secretory Contactin 4 protein | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 蘇剛毅(Kang-Yi Su),潘思樺(Szu-Hua Pan),蔡明宏(Ming-Hung Tsai) | |
dc.subject.keyword | 大腸直腸癌,Contactin 4,血管新生,uPA,細胞增生,分泌型 CNTN4, | zh_TW |
dc.subject.keyword | Colorectal cancer,Contactin 4,Angiogenesis,uPA,Cell proliferation,Secretory CNTN4, | en |
dc.relation.page | 64 | |
dc.identifier.doi | 10.6342/NTU201702204 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2017-08-03 | |
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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