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論文名稱 Title |
轉錄因子prox1調控人類大腸直腸癌表皮細胞-間質轉化作用 The Transcription Factor Prox1 Induces Epithelial-Mesenchymal Transition in Human Colorectal Cancer Cells |
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系所名稱 Department |
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畢業學年期 Year, semester |
語文別 Language |
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學位類別 Degree |
頁數 Number of pages |
82 |
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研究生 Author |
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指導教授 Advisor |
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召集委員 Convenor |
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口試委員 Advisory Committee |
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口試日期 Date of Exam |
2010-07-29 |
繳交日期 Date of Submission |
2010-08-16 |
關鍵字 Keywords |
大腸直腸癌、表皮細胞-間質轉化作用 colorectal cancer, microRNA, prox1, E-cadherin, EMT |
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統計 Statistics |
本論文已被瀏覽 5631 次,被下載 0 次 The thesis/dissertation has been browsed 5631 times, has been downloaded 0 times. |
中文摘要 |
摘要 Prox1 屬於homeobox gene family,其功能為轉錄因子,並發現和Drosophila的 prospero 有同源性,因此命名為 prospero- related homeobox 1。Prox1 被發現在生物體生長發育中扮演重要角色,目前發現 prox1會參與角膜、肝臟、胰,以及神經系統發育的調控中。除此之外,prox1被認為在淋巴管發育中,是主要的調控因子之一。在腫瘤研究中,prox1 在 hepatocellular carcinoma 和乳癌中,被認為是扮演抑制腫瘤的角色。但是,在大腸癌中 prox1 卻有大量表現的情形,並且會促進腫瘤惡化。在研究中發現,於低表現 prox1的 DLD-1 大腸癌細胞中,prox1 大量表現 E-cadherin 轉錄後修飾會受到影響,降低 E-cadherin 的表現量,進而引發 epithelia- mesenchymal transition,同時也會讓細胞貼附能力下降,以及細胞侵犯性增加。另一方面,在SW620大腸癌細胞中,抑制prox1表現,則增加E-cadherin表現量,並且增加細胞貼附能力,以及降低細胞侵犯性。因此,轉錄因子prox1在大腸癌中,參與腫瘤轉移過程的調控,被認為是一個oncogene。 |
Abstract |
Abstract The homeobox gene prox1 is a transcription factor related to the Drosophila gene Prospero. It play an essential role in the development of central nervous system, lens, liver and pancreas. In addition, prox1 is a master gene controlling the early development of the lymphatic vasculature. In tumorigenesis, prox1 has been shown to function as a tumor suppressor gene in hepatocellular carcinoma and breast cancer. Conversely, prox1 is over-expressed in the majority of colorectal cancer (CRC) and it promotes dysplasia, tumor growth and malignant progression. I report the findings here and show that ectopic expression of prox1 in prox1-null DLD-1 colon cancer cells will increase cell invasion but decrease cell adhesion. In addition, prox1 may induce epithelia- mesenchymal transition (EMT) by attenuating E-cadherin expression and up-regulating other EMT markers. On the contrary, knockdown of prox1 increases E-cadherin expression in SW620 cells; reduction of prox1 increases cell adhesion but decreases invasion. In short, the transcription factor prox1 plays an oncogenic role and promotes cancer metastasis in CRC. |
目次 Table of Contents |
目錄 中文摘要 --------------------------------------1 英文摘要 --------------------------------------2 縮寫語 --------------------------------------3 研究背景 --------------------------------------4 研究目的 --------------------------------------8 實驗材料與方法 ---------------------------------9 實驗結果 --------------------------------------32 討論 --------------------------------------37 圖 --------------------------------------40 表 --------------------------------------60 參考文獻 --------------------------------------62 附件 --------------------------------------66 |
參考文獻 References |
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A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci U S A 105, 13556-13561. 34. Dadras, S.S., Skrzypek, A., Nguyen, L., Shin, J.W., Schulz, M.M., Arbiser, J., Mihm, M.C., and Detmar, M. (2008). Prox-1 promotes invasion of kaposiform hemangioendotheliomas. J Invest Dermatol 128, 2798-2806. |
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