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博碩士論文 etd-0202113-222947 詳細資訊
Title page for etd-0202113-222947
論文名稱
Title
Chibby及β-catenin基因表現與子宮頸上皮細胞癌化之研究
Expression of Chibby and β-catenin in malignant trasformation of cervical epithelium
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
56
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2013-01-30
繳交日期
Date of Submission
2013-02-02
關鍵字
Keywords
組織化學免疫染色、基因表現、石蠟包埋組織、β-catenin、Chibby
gene expression, paraffin-embedded tissue, Chibby, β-catenin, Immunohistochemistry
統計
Statistics
本論文已被瀏覽 5655 次,被下載 1604
The thesis/dissertation has been browsed 5655 times, has been downloaded 1604 times.
中文摘要
Wnt/β-catenin訊息傳遞路徑在細胞增殖與細胞分化過程中扮演重要的角色,它可能參與癌化的過程目前已被廣泛探討。而在這個訊息傳遞路徑中,另一個Chibby蛋白,其基因座落在第22號染色長臂(22q12-q13),蛋白產物為126 胺基酸,被發現可以拮抗Wnt訊號路徑的作用。基本上,Chibby 核蛋白可以調控β-catenin的轉錄活性與功能。最近的研究顯示,Chibby可能是一個抑癌基因,在不同的癌症組織或癌細胞株中可以看到Chibby明顯調降,這或許與癌症的惡化有關。因此,我們將之前已經收集(2005-2010)的不同病理特徵的子宮頸石蠟包埋檢體 (包含Normal cervix,CIN 1,CIN 2,CIN 3及Invasive squamous cell carcinoma),以real-time PCR偵測Chibby以及β-catenin mRNA表現,再以組織免疫化學染色偵測Chibby及β-catenin蛋白的表現及在細胞內分佈的位置。分析Chibby、β-catenin表現與子宮頸癌及不同程度的癌前病變有無相關,或是與病人的預後是否相關。本研究結果顯示,Chibby在細胞核及細胞質中的表現和β-catenin的表現並無相關性;Chibby的表現和子宮頸癌惡化程度有關;和正常子宮頸組織比較,子宮頸癌檢體中Chibby在細胞核及細胞質中的表現是調降的,而且病變的程度越高,Chibby的調降情形越明顯,因此認為Chibby的確可以在子宮頸癌中扮演腫瘤抑制蛋白角色。而β-catenin mRNA的表現情形也可以用來評估子宮頸癌惡化程度。
Abstract
Wnt/β-catenin signaling pathway has been mentioned that plays an important role in cell-proliferation and cell-differentiation, which has been widely implicated and documented in associated with carcinogenesis. Within this pathway, another protein, Chibby, is located at chromosome 22q12-q13 and consisted of 126 amino acids, is discovered to antagonist the Wnt/β-catenin signaling. Recently, Chibby has been suggested as a putative tumor suppressor gene, and it is usually down-regulated in different types of cancer or cell lines which may be associated with tumorigenesis. Therefore, we had collected the paraffin-embedded sections of cervix (2005-2010) with different pathological features (Normal cervix, CIN 1, CIN 2, CIN 3, Invasive squamous cell carcinoma). These samples were subject to detect mRNA expression levels of Chibby and β-catenin by real-time PCR technique, and measured for protein expression and cellular localization of Chibby and β-catenin using immunohistochemistry. The expression of Chibby and β-catenin were analyzed for possible association with disease progression of cervical cancer, as well as patients’ prognosis. In this study, the cytoplasmic and nuclear expressions of chibby were not correlated with the cytoplasmic and nuclear localization of β-catenin. Both nuclear and cytoplasmic expressions of chibby were reduced in cervical cancers, and down-regulation of Chibby was associated with advanced disease of cervical cancer, indicating it may be a putative tumor suppressor in cervical cancer. β-catenin mRNA expression is also a biomarker for evaluating the disease progression of cervical cancer.
目次 Table of Contents
中文摘要………………………………………..……………………… 1
英文摘要………………………………………..……………………… 2
前言…………………………………………………………………….. 3
研究動機…………………………………………..…………………… 8
材料與方法………………………………………..…………………… 9
結果……………………………………………………………………. 15
討論……………………………………………………………………. 18
結論……………………………………………………………………. 22
未來展望……………………………………………………….…….. 23
圖表…………………………………………………………………… 24
附圖…………………………………………………………………… 42
參考文獻……………………………………………………….…….. 47
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