WWOX基因调控肿瘤细胞生长与免疫抑制研究
发布时间：2018-08-08 21:09
【摘要】： 包含WW域的氧化还原酶(WWOX)基因是一种染色体脆性位点基因,表达在多种正常组织的上皮细胞中,而在肿瘤组织中则表现为表达降低或缺失。研究表明,WWOX在细胞凋亡中发挥了重要作用,WWOX表达降低增加了细胞对致癌因素的敏感性,与恶性肿瘤的发生发展密切相关。 本研究在构建携带WWOX基因全编码序列的真核表达载体pcDNA4.0/Myc-His-WWOX基础上,采用RT-PCR、Western blot方法验证了WWOX在肿瘤细胞中的表达;经流式细胞仪、MTT法检测证实WWOX基因转染后,肿瘤细胞发生生长抑制、凋亡以及免疫抑制效应降低等变化;采用半定量RT-PCR、免疫组化染色方法检测相关基因表达,结果显示WWOX基因转染可调控与细胞周期、凋亡以及免疫抑制相关的多种基因的表达;WWOX基因体内转染亦具有明显的抑瘤效应和免疫调节作用。 本研究结果提示WWOX具有转录因子功能,可以通过调控多种基因表达来发挥抑制肿瘤细胞生长、诱导肿瘤细胞凋亡、降低肿瘤细胞的免疫抑制效应等作用。WWOX基因调控免疫抑制功能的首次发现,丰富了对WWOX生物学功能的认识,为进一步研究WWOX的抗肿瘤活性提供新的资料。
[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.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2008
【分类号】：R392;R730.5
本文编号：2173043
[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.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2008
【分类号】：R392;R730.5
【参考文献】
相关期刊论文 前2条
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2 李峰,陈临溪;细胞周期蛋白D与细胞周期调控研究进展[J];国外医学(生理、病理科学与临床分册);2005年03期
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