【摘要】： 包含WW域的氧化還原酶(WWOX)基因是一種染色體脆性位點(diǎn)基因,表達(dá)在多種正常組織的上皮細(xì)胞中,而在腫瘤組織中則表現(xiàn)為表達(dá)降低或缺失。研究表明,WWOX在細(xì)胞凋亡中發(fā)揮了重要作用,WWOX表達(dá)降低增加了細(xì)胞對(duì)致癌因素的敏感性,與惡性腫瘤的發(fā)生發(fā)展密切相關(guān)。 本研究在構(gòu)建攜帶WWOX基因全編碼序列的真核表達(dá)載體pcDNA4.0/Myc-His-WWOX基礎(chǔ)上,采用RT-PCR、Western blot方法驗(yàn)證了WWOX在腫瘤細(xì)胞中的表達(dá);經(jīng)流式細(xì)胞儀、MTT法檢測(cè)證實(shí)WWOX基因轉(zhuǎn)染后,腫瘤細(xì)胞發(fā)生生長抑制、凋亡以及免疫抑制效應(yīng)降低等變化;采用半定量RT-PCR、免疫組化染色方法檢測(cè)相關(guān)基因表達(dá),結(jié)果顯示W(wǎng)WOX基因轉(zhuǎn)染可調(diào)控與細(xì)胞周期、凋亡以及免疫抑制相關(guān)的多種基因的表達(dá);WWOX基因體內(nèi)轉(zhuǎn)染亦具有明顯的抑瘤效應(yīng)和免疫調(diào)節(jié)作用。 本研究結(jié)果提示W(wǎng)WOX具有轉(zhuǎn)錄因子功能,可以通過調(diào)控多種基因表達(dá)來發(fā)揮抑制腫瘤細(xì)胞生長、誘導(dǎo)腫瘤細(xì)胞凋亡、降低腫瘤細(xì)胞的免疫抑制效應(yīng)等作用。WWOX基因調(diào)控免疫抑制功能的首次發(fā)現(xiàn),豐富了對(duì)WWOX生物學(xué)功能的認(rèn)識(shí),為進(jìn)一步研究WWOX的抗腫瘤活性提供新的資料。
[Abstract]:The oxidoreductase (WWOX) gene, which contains the WW domain, is a chromosome fragile site gene expressed in the epithelial cells of a variety of normal tissues, while in the tumor tissue the expression is reduced or missing. The study shows that WWOX plays an important role in the apoptosis, and the decrease in WWOX table increases the sensitivity of the cell to the carcinogenic factors. The occurrence and development of malignant tumors are closely related.
In this study, based on the construction of a eukaryotic expression vector carrying the full encoding sequence of WWOX gene pcDNA4.0/Myc-His-WWOX, the expression of WWOX in the tumor cells was verified by RT-PCR and Western blot. The growth inhibition, apoptosis and immunosuppression effect of the tumor cells were confirmed by the flow cytometry and MTT method. The expression of related genes was detected by semi quantitative RT-PCR and immunohistochemical staining. The results showed that the transfection of WWOX gene could regulate the expression of various genes related to cell cycle, apoptosis and immunosuppression, and the transfection of WWOX gene in vivo also had obvious tumor suppressor effect and immunomodulatory effect.
The results of this study suggest that WWOX has the function of transcription factor, which can play the role of inhibiting the growth of tumor cells, inducing tumor cell apoptosis and reducing the immunosuppressive effect of tumor cells by regulating a variety of gene expression. The first discovery of the immune suppression function of.WWOX gene can be found, and the understanding of the biological function of WWOX is enriched. The study of the antitumor activity of WWOX provides new information.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2008
【分類號(hào)】：R392;R730.5

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