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    題名: 眼翳中E-cadherin啟動子過度甲基化會造成E-cadherin蛋白不活化
    E-cadherin promoter hypermethylation may contribute to protein inactivation in pterygium
    作者: 邱育德;Yu-Te Chiu
    貢獻者: 醫學院臨床醫學研究所碩士班
    關鍵詞: 眼翳;E-cadherin;β-catenin;pterygium;E-cadherin;β-catenin
    日期: 2010
    上傳時間: 2010-09-29 12:17:05 (UTC+8)
    摘要: 眼翳中E-cadherin啟動子過度甲基化會造成E-cadherin
    蛋白不活化
    摘要
    背景: 目前相關的研究認為眼翳可能不僅是過去所認為的組織變性,
    其特性與腫瘤細胞相似。所以我們假設眼翳與腫瘤細胞可能有相似的機轉,而很多研究發現E-cadherin及其相關的蛋白在腫瘤細胞中表現量減少,且與基因啟動子過度甲基化有關,這樣的現象會導致腫瘤細胞轉移及預後不良。雖然曾有研究發現E-cadherin在眼翳也有減少的現象,但很少有文獻解釋其相關的機轉,所以這篇研究的目地在分析眼翳中「E-cadherin蛋白不活化」是否和「E-cadherin基因啟動子過度甲基化」有關,並探討眼翳可能的生成機轉。
    研究方法: 實驗組包含120位眼翳患者,其中70位男性及50位女性,平均62.5歲,共收集120片眼翳組織,而控制組包含15位男性及15位女性,平均62.8歲,共收集30片正常結膜組織,利用免疫組織染色法(Immunohistochemistry)分析E-cadherin、β-catenin蛋白表現,利用methyl-specific PCR(MS-PCR)評估E-cadherin啟動子甲基化程度。
    實驗結果: 在實驗組中,有32個(26.7%)檢體呈現E-cadherin基因啟動子過度甲基化。在這120個眼翳檢體裡,有79個(65.8%)檢體,有表現E-cadherin蛋白,有41個(34.2%)檢體不表現,而「E-cadherin基因啟動子過度甲基化」與「E-cadherin蛋白表現」間呈現負相關(P<0.0001) 。此外,當E-cadherin蛋白不表現時,β-catenin呈現異常分布(非細胞膜分布)的比例較高(P<0.0001) 。
    結論: 我們的研究發現: E-cadherin基因啟動子過度甲基化會抑制眼翳
    中E-cadherin蛋白的表現,當E-cadherin蛋白表現量下降時,會導致β-catenin呈現異常分布於細胞質與細胞核,由於β-catenin異常分布於細胞核會與細胞增生(proliferation)相關,而眼翳目前也被認為是一種細胞增生的疾病,所以我們認為「E-cadherin基因啟動子過度甲基化」可能在眼翳的生成機轉中,扮演一重要的角色。

    E-cadherin promoter hypermethylation may contribute to protein inactivation in pterygium

    Abstract

    Background

    Our recent reports indicated that the molecular changes of pterygium are like tumor cells. We assume that pterygium may have this similar mechanism in oncogenesis. Some studies have revealed that E-cadherin associated protein expression decreases in many tumors and pterygium. It may be a marker for tumor metastasis and prognosis. However, there were limited studies examining the reason for E-adhesion protein inactivation in pterygium. Therefore, the aim of this study was to analyze the association of E-cadherin promoter hypermethylation with protein inactivation in pterygium tissues.

    Material and Method

    The E-cadherin methylation-status and the expression of E-cadherin and β-catenin protein were studied using methylation-specific PCR and immunohistochemistry respectively on 120 pterygial specimens and 30 normal conjunctivas.

    Result

    There were 79 (65.8%) pterygial specimens positive for E-cadherin protein expression and 41 (34.2%) specimens were negative. The E-cadherin staining was limited to the membrane of the epithelial layer. Hypermethylation of E-cadherin gene promoter was detected in 32 (26.7%) of the 120 pterygial specimens. There was a reverse correlation between E-cadherin gene promoter hypermethylation and E-cadherin protein expression (p<0.0001). In the E-cadherin negative group, aberrant localization of β-catenin was higher.

    Conclusion

    Our study demonstrates E-cadherin gene promoter hypermethylation suppresses the expression of E-cadherin protein. Moreover, loss of E-cadherin protein may contribute to aberrant localization of β-catenin. These data provide evidence that methylation exists in pterygium and may play a role in the development of pterygium.
    顯示於類別:[臨床醫學研究所] 博碩士論文

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