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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃銓珍 | |
| dc.contributor.author | Wen-Hsin Peng | en |
| dc.contributor.author | 彭文欣 | zh_TW |
| dc.date.accessioned | 2021-05-20T20:42:50Z | - |
| dc.date.available | 2009-07-23 | |
| dc.date.available | 2021-05-20T20:42:50Z | - |
| dc.date.copyright | 2008-07-23 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-07-22 | |
| dc.identifier.citation | 參考文獻
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Vav3 oncogene activates estrogen receptor and its overexpression may be involved in human breast cancer. BMC Cancer 8: 158. 44 Lewis J (2007). Molecular biology of the cell. Garland Science ; Taylor & Francis [distributor]: New York; London. Liu CA, Wang MJ, Chi CW, Wu CW, Chen JY (2004a). Overexpression of rho effector rhotekin confers increased survival in gastric adenocarcinoma. J Biomed Sci 11: 661-70. Liu CA, Wang MJ, Chi CW, Wu CW, Chen JY (2004b). Rho/Rhotekin-mediated NF-kappaB activation confers resistance to apoptosis. Oncogene 23: 8731-42. Lundquist EA (2006). Small GTPases. WormBook: 1-18. Macdonald JS (2006). Gastric cancer--new therapeutic options. N Engl J Med 355: 76-7. Master SS (2004). Gastric carcinoma. Dis Mon 50: 532-9. Ming SC (1977). Gastric carcinoma. A pathobiological classification. Cancer 39: 2475-85. Neugut AI, Hayek M, Howe G (1996). Epidemiology of gastric cancer. Semin Oncol 23: 281-91. Ng K, Meyerhardt JA, Fuchs CS (2007). 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Nat Cell Biol 4: E97-100. Weinberg RA (2007). The biology of cancer. Garland Science: New York. Wright WE, Pereira-Smith OM, Shay JW (1989). Reversible cellular senescence: implications for immortalization of normal human diploid fibroblasts. Mol Cell Biol 9: 3088-92. Yamaguchi Y, Katoh H, Yasui H, Mori K, Negishi M (2001). RhoA inhibits the nerve growth factor-induced Rac1 activation through Rho-associated kinase-dependent pathway. J Biol Chem 276: 18977-83. 行政院衛生署. 台北. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/9812 | - |
| dc.description.abstract | 胃癌全球罹患率與致死率皆高居癌症的第二位，但我們對胃癌之致病機轉了解仍有限。實驗室以差異性表現分析，發現Rhotekin (RTKN) 蛋白在胃癌組織中表現量高於週邊正常組織。目前對於 RTKN 的功能研究知道其會和 Rho、 Tax interacting protein-1 一起促進 serum response elememt 的活化，而我們實驗室之前則發現有RTKN 大量表現的細胞具有抗凋亡的能力可能是因 RTKN 影響NF-κB的活性，另外也發現 RTKN 降低了 RhoA 下游 ROCK 的活性並造成Rac 活性上升而影響細胞骨架的重整，減少 stress fiber 生成並增加細胞 surface protrusion 和移動的能力。在本論文中，我們進一步探討 RTKN 在細胞轉型(cell transformation)
及遷移(migration)過程中所扮演的角色。我們根據細胞株中所擁有RTKN 的表現量挑選出合適的細胞株，分別在低表現量的細胞株(H1299, AZ-521)內大量表現RTKN以及在高表現量的細胞株(NUGC-3)內利用sh-RNA 專一性抑制內生性的RTKN 之表現。初步發現，過度表現RTKN 使得細胞喪失接觸性抑制(contact inhibition of growth)而造成細胞飽和度增加，促使細胞骨架重整造成細胞型態改變，增加細胞 遷移(Migration)及細胞入侵(Invasion)之能力，並且發現細胞過度表現RTKN 促進其非固著性依賴生長(anchorage-independent growth)之能力。這些現象說明了RTKN 參與了細胞轉型(transformation)及遷移(migration)，因此可能與胃癌生成以 及轉移惡化有關。我們藉由本研究之分析RTKN 所給予細胞轉型之特性，建議RTKN 於胃癌生成或惡化中扮演一重要的角色及可能之機制。 | zh_TW |
| dc.description.abstract | Gastric cancer is ranked the fourth common cancer and the second leading cause of
cancer death worldwide (almost 1 million deaths/year).Using ordered differential display, we have identified rhotekin, the gene encoding Rho effector rhotekin (RTKN) as one of the genes overexpressed in human gastric cancer. To further understand the role of Rho/RTKN involved in the pathogenic development of GC, in this study, we propose to dissect Rho signaling pathways that are mediated by RTKN, and special efforts will be focused on the ones contribute to malignant transformation and tumor metastasis. To assess the function of RTKN in cellular transformation, we ectopically expressed RTKN in cultured cell, and monitored the biological readouts of RTKN expression. The data shown, RTKN expression suppressed contact inhibition of movement in both H1299 as well as HEK293 cells. RTKN In consistence, overexpression of RTKN conferred an increased saturation density in H1299 cells. Overexpression induced extensive cell surface protrusions with a concomitant decrease of stress fibers and focal adhesions. We have further generated stable clones : H1299 and AZ-521, RTKN low expresser that stably expressed RTKN, and NUGC-3 , RTKN high expresser that stably knock downed RTKN, and tested for transforming activity. The stable clone displayed increased migration and invasion ability when compared to the parental cells. In addition, the stable clone developed anchorage-independent growth in soft agar whereas the parental cells showed reduced growth in soft agar. Taken together, we conclude that overexpression of RTKN may promote cell transformation and cell migration, and thus and thus contribute to tumor metastasis. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-20T20:42:50Z (GMT). No. of bitstreams: 1 ntu-97-R95b46012-1.pdf: 19732550 bytes, checksum: ae398acf4dfecb4d586e88e827bf1d9d (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | 目 錄
項目 頁碼 目錄 Ⅰ 圖目錄 Ⅳ 縮寫表 Ⅵ 中文摘要 Ⅶ 英文摘要 Ⅷ 第一章 緒論 1 第一節 胃癌之簡介 1 第二節 癌症之生成 5 第三節 Rhotekin(RTKN) 10 第二章 研究目標 12 第三章 材料與方法 13 第一節 細胞培養 (Cell culture) 13 第二節 西方墨點轉漬分析 (Western blot) 14 第三節 轉染反應 (Transfection) 15 第四節 製備穩定細胞株 (stable clone) 16 第五節 免疫螢光染色 (Immunofluorescence stain) 17 II 第六節 細胞飽和度測試 18 第七節 細胞增生分析 (WST-1 assay) 18 第八節 反轉錄聚合酶連鎖反應 (RT-PCR) 19 第九節 基質金屬酶(MMP)酶譜法 (Zymography) 20 第十節 細胞遷移與入侵能力測試 (Migration and Invasion assay) 21 第十一節 洋菜軟膠方法(Soft agar assay)分析非固著依賴性細胞生 長(Anchorage-independent growth assay, AIG) 22 第四章 結果 24 第一節 探討RTKN 對細胞轉型之影響 24 (一) 過度表現RTKN 使細胞喪失接觸性抑制(contact inhibition of growth)而造成細胞飽和度增加 24 (二) 過度表現RTKN 對於細胞生長速率之影響 25 (三) 過度表現RTKN 使細胞型態改變 26 (四) 過度表現RTKN 對細胞骨架之影響 27 (五) 過度表現RTKN 增加細胞遷移(Migration)及細胞入 侵(Invasion)之能力 28 (六) 分析RTKN 穩定細胞株中MMP 之含量及活性 29 (七) 細胞過度表現RTKN 促進其非固著性依賴生長 (anchorage-independent growth)之能力 30 第二節 探討胃癌細胞中RTKN 的含量對細胞轉型之影響 31 (一) 於AZ-521 胃癌細胞株中過度表現RTKN 31 (二) 於NUGC-3 胃癌細胞株中剔除RTKN 之表現 32 第五章 討論 34 III 第一節 探討RTKN 促使細胞飽和度增加 34 第二節 探討RTKN 使細胞型態改變並且造成細胞骨架之重整 35 第三節 探討RTKN 增加細胞遷移 (Migration)及細胞入侵 (Invasion)之能力 36 第四節 探討RTKN 促進細胞非固著性依賴生長 (Anchorage-independent growth)之能力 38 參考文獻 40 圖 46 附錄 67 附表一、本研究所使用之質體DNA 67 附表二、H1299/RTKN 穩定表現細胞株之特性 68 附圖一、RTKN過度表現不影響組成粘著斑蛋白質之表現 69 附圖二、Boyden chamber 結構示意圖 70 | |
| dc.language.iso | zh-TW | |
| dc.title | 探討Rhotekin基因於癌症病變過程中所扮演的角色 | zh_TW |
| dc.title | To study the oncogenic role of Rhotekin, a RhoGTPase effector | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 張久瑗 | |
| dc.contributor.oralexamcommittee | 周玉山 | |
| dc.subject.keyword | 癌症,細胞轉型,細胞遷移,細胞入侵,非固著性依賴生長, | zh_TW |
| dc.subject.keyword | Cancer,Cell transformation,Cell migration,Cell invasion,Anchorage-independent growth, | en |
| dc.relation.page | 70 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2008-07-22 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科學研究所 | zh_TW |
| 顯示於系所單位： | 生化科學研究所 | |
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