E-CADHERIN訊息傳遞路徑與翼狀贅片形成之相關性研究

中國醫藥大學機構典藏 China Medical University Repository, Taiwan > 醫學院 > 醫學系 > 研究計畫 > Item 310903500/13284

請使用永久網址來引用或連結此文件: http://ir.cmu.edu.tw/ir/handle/310903500/13284

題名:	E-CADHERIN訊息傳遞路徑與翼狀贅片形成之相關性研究
其他題名:	Study of the Correlation of E-Cadherin Signal Pathway and Pterygium
作者:	蔡宜佑(Yi-Yu Tsai)
貢獻者:	醫學院醫學系學士班眼科學科;中國附醫眼科部
日期:	2009-07-31
上傳時間:	2009-09-01 16:18:33 (UTC+8)
摘要:	翼狀贅片是一種在結膜表面有不正常楔形膜狀增生，其範圍可以包括眼白部分和眼瞼內側的組織，與長期紫外線輻射UV-A 及 UV-B 有相當關聯，在熱帶或陽光充足的地帶角膜翼狀贅片發生率較高。角膜翼狀贅片大部份在鼻側眼裂部球結膜的尖端向著角膜呈三角形侵入的狀態。若達到瞳孔中心區的話，會引起視力障礙，需要手術切除治療。翼狀贅片在結膜表面之不正常楔形膜狀增生之特性與腫瘤細胞極為相似，本研究室過去分析 p53 抑癌基因在翼狀贅片的表現，除偵測到其蛋白過度表現外亦偵測到p53 基因的突變，因此推測此種不正常的楔形膜狀增生可能與細胞癌化有相同的分子機轉，但此楔形膜狀增生與癌細胞最大的差異主要在於不具侵入組織及轉移至其他器官的能力。最近研究在許多的腫瘤研究中均發現E-cadherin 表現量的減少，並可作為患者是否發生轉移及預後的評估指標。已知E-cadeherin 需與α-catenin、β-catenin 及p120ctm 結合形成複合體鑲嵌於細胞膜上才具有生物功能。過去已知以ligand 活化EGFR 路徑可使caterin 磷酸化而使 E-cadherin–catenin 分解，β-catenin 是Wnt 訊息傳遞的家族成員之一，細胞質內未和 cadherins 形成複合體的β-catenin 會轉與成長因子－Wnt 作用並進入細胞核中，促進細胞的增生與分化，導致腫瘤細胞之增生(proliferation)及轉移(metastasis)現象。本研究室初步利用免疫組織化學染色分析E-cadherin 在30 位翼狀贅片患者手術切除之楔形膜狀增生組織，結果發現高達40%的不表現率，因此本計劃擬以免疫組織化學染色法分析異狀墜片組織中E-cadeherin、α-catenin、β-catenin 及p120ctm 蛋白的表現情形及位置，以瞭解是否由於E-cadherin 複合體的表現異常而促進細胞增生。E-cadeherin 訊息傳遞路徑的異常除了造成細胞增生外亦會改變細胞的轉移及侵入(invasion)能力，而在翼狀贅片組織中 E-cadeherin 訊息傳遞路徑的異常卻只會造成細胞增生而不會轉移。為瞭解此分子機制本研究第二年擬利用本研究室以初帶培養所建立的翼狀贅片細胞以ligand 處理後分析Wnt 調控路徑的活化情形，同時以反轉錄定量聚合.連鎖反應分析下游基因的表現，並分析細胞migration 及invasion 的能力，以瞭解E-cadeherin 及Wnt 訊息傳遞路徑在翼狀贅片型成過程所扮演的角色，並將此結果與腫瘤細胞做比較，找出異狀贅片細胞與可轉移之惡性腫瘤細胞在Wnt 訊息傳遞路徑的差異，本計畫的執行成果將除可瞭解翼狀墜片不正常增生之分子積轉亦能對如何抑制腫瘤細胞的轉移提供可行的解決方針。 Pterygium is a chronic condition characterized by the encroachment of a fleshy triangle of conjunctiv al tissue into the cornea. Epidemiological evidence suggests that UV irradiation plays the most important role. In our previous studies, abnormal levels of the p53 protein being found in pterygial epithelium. Mutations in the p53 gene could lead to tumor formation and have been found in various types of tumor cells. We assume that pterygium may have the similar mechanism in oncogenesis. However, the most different in pterygial cell and other cancer cells is that pterygium does not have the activity of invasion and metastasis. Recently, many studies revealed that E-cadherin expression decreases in many tumors, and it may be a marker for tumor metastasis and prognosis. We already known that E-cadherin has no bioactivity until binding on cell membrane as a complex with α-catenin、β-catenin and p120ctm . It has been well understood that ligand can active EGFR pathway and phosphorylate ceterin to digest E-cadherin. β-catenin is one part of Wnt family in signal transduction. Unconjugated β-catenin in cytoplasma will interactive with Wnt and get into cell nucleus, resulting in cell proliferation and tumor cell metastasis. In our study, we use immunohistochemistry to analyze the E-cadherin in 30 pterygial samples and the unexpression rate up to 40%. Therefore, we try to using immunohistochemistry to analyze the protein expression in E-cadherin、α-catenin、β-catenin and p120ctm in pterygium, to investigate if the abnormal expression in E-cadherin complex will cause cell proliferation. E-cadherin signal pathway not only causes cell proliferation but also changes the activity of cell invasion. However, E-cadherin signal pathway only results in cell proliferation but no metastasis in pterygium. To investigate this, in our second year plan, we use cultured pterygium cell and analyze the process of the Wnt signal pathway, also analyzing the gene expression by PCR. We try to investigate the role of E-cadherin and Wnt in pterygium formation, also compare with other tumor cell and find out the difference between each other. Our study result could give more information about the pterygium formation, and also offer a solution in suppressing tumor metastasis.
顯示於類別:	[醫學系] 研究計畫

文件中的檔案:

檔案	描述	大小	格式	瀏覽次數
index.html		0Kb	HTML	248	檢視/開啟

在CMUR中所有的資料項目都受到原著作權保護.

TAIR相關文章

資料載入中.....