【摘要】：bitl基因是2004年研究整合素對Bcl-2的表達調(diào)控時發(fā)現(xiàn)的一個新基因，因其具有下調(diào)Bcl-2表達的功能而命名為bitl(bcl-2 inhibitor of transcription 1)。后來的基因組研究表明，從細菌到人類Bitl在進化上是高度保守的。在人體組織內(nèi)，Bitl在睪丸、前列腺、骨骼肌及肝臟高表達，在心臟、脾、胎盤及結(jié)腸有表達，人胸腺及外周血白細胞中幾乎檢測不到它的表達。Bitl蛋白定位于線粒體內(nèi)膜；胞漿內(nèi)Bitl濃度的升高可以明顯促進細胞凋亡的發(fā)生，而其濃度的降低可以減少細胞凋亡的發(fā)生。也就是說，Bitl蛋白是一種與細胞凋亡密切相關的新分子，因此，研究這種具有促凋亡作用的線粒體蛋白對于探索凋亡的發(fā)生和調(diào)節(jié)具有重要意義。本研究旨在觀察該蛋白在人婦科腫瘤細胞中的分布及生物學作用，并初步探討其作用機制，以期為婦科腫瘤的治療提供一些新的思路。 本課題研究可以分為以下三個部分： (一) 應用組織芯片技術分析Bitl在婦科腫瘤中的分布 方法：應用組織芯片技術，通過免疫組織化學方法比較84例宮頸癌標本和76例正常宮頸組織標本中Bitl的表達情況，以及82例卵巢癌標本和78例正常卵巢組織標本中Bitl的表達情況。 結(jié)果：經(jīng)過統(tǒng)計學分析，發(fā)現(xiàn)Bitl在宮頸癌和正常宮頸組織中的表達無顯著性差異，在不同的宮頸癌病理分級中也無顯著的統(tǒng)計學差異；而Bitl在卵巢癌組織中的表達卻顯著高于正常卵巢組織，并且隨著病理分級的增加，Bitl的表達水平顯著降低。鑒于這種差異表達，我們選取卵巢癌作為研究模型。 (二) 觀察人Bitl蛋白促卵巢癌細胞凋亡的作用 方法：首先構(gòu)建pCMV-Mye-bitl和pCMV-Mye-EGFP真核表達載體，，
[Abstract]:Bitl gene is a new gene which was discovered in 2004 when studying the regulation of Bcl-2 expression by integrin. It was named bitl (bcl-2 inhibitor of transcription 1) because of its function of down-regulating the expression of Bcl-2. Later genomic studies showed that Bitl, from bacteria to humans, was highly conserved in evolution. Bitl was highly expressed in testis, prostate, skeletal muscle and liver, and expressed in heart, spleen, placenta and colon. The increase of the concentration of Bitl in the cytoplasm can obviously promote the occurrence of apoptosis, and the decrease of the concentration of Bitl can reduce the occurrence of apoptosis. That is to say, Bitl protein is a new molecule closely related to apoptosis. Therefore, it is important to study this mitochondrial protein which can promote apoptosis in order to explore the occurrence and regulation of apoptosis. The purpose of this study was to observe the distribution and biological function of the protein in human gynecologic tumor cells and to explore its mechanism so as to provide some new ideas for the treatment of gynecological tumors. The research can be divided into the following three parts: (1) the distribution of Bitl in gynecological tumors was analyzed by tissue chip technique. Methods: using tissue chip technology, The expression of Bitl in 84 cases of cervical carcinoma and 76 cases of normal cervical tissue was compared by immunohistochemical method, and the expression of Bitl in 82 cases of ovarian cancer and 78 cases of normal ovarian tissue was compared. Results: there was no significant difference in the expression of Bitl between cervical cancer and normal cervix, and there was no significant difference in pathological grade of cervical cancer. However, the expression of Bitl in ovarian cancer tissues was significantly higher than that in normal ovarian tissues, and decreased with the increase of pathological grade. In view of this differential expression, we selected ovarian cancer as the study model. (2) to observe the effect of human Bitl protein on apoptosis of ovarian cancer cells. Firstly, the eukaryotic expression vectors of pCMV-Mye-bitl and pCMV-Mye-EGFP were constructed.
【學位授予單位】：第四軍醫(yī)大學
【學位級別】：博士
【學位授予年份】：2006
【分類號】：R346

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