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作 者:李静[1,2] 林河春[1,2] 张方淋[1,2] 于静娴[1,2] 萨冰清[1,2] 刘蕾[1,2] 闫明霞[1,2] 姚明[1,2]
机构地区:[1]上海交通大学医学院附属仁济医院 [2]上海市肿瘤研究所癌基因及相关基因国家重点实验室,上海200032
出 处:《肿瘤》2012年第3期164-169,共6页Tumor
基 金:国家重点基础研究发展计划(973计划)资助项目(编号:2009CB521803);上海市科学技术委员会科研计划资助项目(编号:09140902000;10140902401)
摘 要:目的:以人肺癌低转移细胞株SPC-A-1为对照,分析人肺癌高转移细胞株SPC-A-1sci的分子转移机制及其相关的信号通路,寻找肺癌转移的关键基因。方法:应用芯片技术检测人肺癌低转移细胞株SPC-A-1和高转移细胞株SPC-A-1sci的差异基因。采用显著性通路分析和构建信号转导网络等生物信息学分析方法寻找肿瘤转移相关的潜在关键基因和信号通路。结果:与SPC-A-1细胞比较,SPC-A-1sci细胞共有上调表达的差异基因2892个,下调表达的差异基因3248个;上调差异基因参与的显著性信号转导通路共有48条,下调差异基因参与的显著性信号转导通路共65条。网络中的关键基因主要是丝裂原活化蛋白激酶1、表皮生长因子受体、AKT1、AKT3、PIK3CD(phosphoinositide-3-kinase,catalytic,delta polypeptide)、PIK3R1[phosphoinositide-3-kinase3,regulatory subunit1(alpha)]、PIK3R3、KRAS和胰岛素样生长因子1受体等。结论:人肺癌高转移细胞株SPC-A-1sci的基因芯片检测和生物信息学分析为肺癌转移的基础研究和临床防治提供了依据。Objective: To analyze the metastatic mechanism and its related molecular signaling pathways in the high-metastatic human lung cancer cell line SPC-A-lsci as compared with the lowmetastatic human lung cancer cell line SPC-A-I as the control, and to find the key genes for lung cancer metastasis. Methods: The differentially expressed genes between the high-metastatic human lung cancer cell line SPC-A-lsci and the low-metastatic human lung cancer cell line SPC-A-1 were detected by microarray. The potential key genes and the related signal pathways in lung cancer metastasis were examined by bioinformatics analyses including pathway analyses and signal transduction networks. Results: As compared with the SPC-A-1 cells, 2 892 genes were up-regulated and 3 248 genes were down-regulated in the SPC-A-lsci cells. There were 48 signal transduction pathways involved in the up-regulated genes and 65 signal transduction pathways involved in the down-regulated genes. The key genes in the signal transduction networks were mitogen-activated protein kinase-1, epidermal growth factor receptor, AKT1, AKT3, phosphoinositide-3-kinase, catalytic, delta polypeptide (PIK3CD), phosphoinositide-3-kinase 3, regulatory subunitl (alpha) (PIK3R1), PIK3R3, KRAS, and insulin-like growth factor-1 receptor. Conclusion: The applications of gene chip technology and bioinformatics tools in the investigation of metastatic mechanism and its related molecular signaling pathways of highmetastatic lung cancer cell line SPC-A-lsci provide evidences for the basic research and the clinical prevention and treatment research for lung cancer metastasis.
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