肝细胞癌中抑制细胞凋亡相关基因的差异表达
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江苏省自然科学基金(BK2004013);南京市医学科技发展项目(ZKX0401)


Comparative analysis of cell apoptosis inhibitory genes involved in hepatoma
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    目的:研究肝癌细胞系的基因表达概况,筛选表达差异的抑制细胞凋亡相关基因,探索肝细胞癌发生发展机制及肝细胞癌治疗的新靶点-方法:通过基因芯片技术检测肝癌细胞系bel-7402-hep-3b与胎儿肝细胞的全基因组序列,筛选表达差异的抑制细胞凋亡相关基因,采用rt-pcr-免疫组化对部分差异表达基因进行了验证-结果:在检测的54 614个探针组中,bel-7402-hep-3b两株肝癌细胞与胎儿肝脏细胞相比表达共同上调2倍及2倍以上的有1 452个基因;表达下调2倍及2倍以上的有2 054个基因-与抑制细胞凋亡相关表达上调的基因有12个,选取2个基因进行rt-pcr-免疫组化验证,结果与基因芯片结论基本一致-结论:肝细胞癌中有众多的抑制细胞凋亡基因表达增高,通过影响tnf通路-bcl-2蛋白等多种方式共同抑制细胞凋亡,促进肿瘤细胞增殖-对这些基因的研究有助于阐明肝细胞癌发生发展机制,为肝细胞癌的治疗提供新的靶点-

    Abstract:

    objective:to explore the profiles of hepatoma cell lines-specific gene expression and identify the differential expressed cell apoptosis inhibitory genes for exploring hepatocarcinogenesis and new therapeutic targets. Methods:the profiles of gene expression of hepatoma cell lines bel-7402,hep-3b and fetal liver cells were analyzed by gene chips. The differential expressed cell apoptosis inhibitory genes were screened. The selected candidate genes were confirmed by rt-pcr in three kinds of cell lines and by immunohistochemistry in 20 specimens of hcc and adjacent noncancerous tissues. Results:of the detected 54 614 probe sets,compared with the fetal liver cells,1 452 genes were up-regulated by more than 2 folds and 2 054 genes were down-regulated by more than 2 folds in the hepatoma cell lines bel-7402 and hep-3b,in which 12 differential expressed cell apoptosis inhibitory genes were screened. The results of rt-pcr showed that the expressions of sodd and survivin in hepatoma cell lines were higher than those in fetal liver cells (p < 0.05). The positive rates of sodd and survivin were significantly higher in hcc than in adjacent noncancerous tissues(65% vs. 15%,and 75% vs. 10%,p < 0.05). Conclusion:many cell apoptosis inhibitory genes were up-regulated in hcc,which can inhibit cancer cell apoptosis and promote cancer cell proliferation by effecting tnf pathway,bcl-2 protein expression and so on. Analysis of these genes can provide important clues for disclosing the mechanisms of hepatocellular carcinoma pathogenesis and supplying possible new therapeutic targets.

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张永臣,叶 伟,文 剑,赵 伟.肝细胞癌中抑制细胞凋亡相关基因的差异表达[J].南京医科大学学报(自然科学版),2009,29(9):1224-1228

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  • 收稿日期:2009-04-17
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