肺癌高转移和低转移细胞株中差异基因的分析
Analysis of differentially expressed genes between the high-metastatic and low-metastatic lung cancer cell lines
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。
肿瘤转移
寡核苷酸序列分析
生物信息学
Lung neoplasms
Neoplasm metastasis
Oligonucleotide sequence analysis
Bioinformatics
Abstract
Objective: To analyze the metastatic mechanism and its related molecular signalingpathways in the high-metastatic human lung cancer cell line SPC-A-1sci as compared with the lowmetastatichuman lung cancer cell line SPC-A-1 as the control, and to find the key genes for lung cancermetastasis. Methods: The differentially expressed genes between the high-metastatic human lungcancer cell line SPC-A-1sci and the low-metastatic human lung cancer cell line SPC-A-1 were detectedby microarray. The potential key genes and the related signal pathways in lung cancer metastasis wereexamined by bioinformatics analyses including pathway analyses and signal transduction networks. Results: As compared with the SPC-A-1 cells, 2892 genes were up-regulated and 3248 genes weredown-regulated in the SPC-A-1sci cells. There were 48 signal transduction pathways involved in theup-regulated genes and 65 signal transduction pathways involved in the down-regulated genes. Thekey genes in the signal transduction networks were mitogen-activated protein kinase-1, epidermalgrowth factor receptor, AKT, AKT3, phosphoinositide-3-kinase, catalytic, delta polypeptide(PIK3CD),phosphoinositide-3-kinase 3, regulatory subunit1(alpha)(PIK3R1), PIK3R3, KRAS, and insulin-likegrowth factor-1 receptor. Conclusion: The applications of gene chip technology and bioinformaticstools in the investigation of metastatic mechanism and its related molecular signaling pathways of highmetastaticlung cancer cell line SPC-A-1sci provide evidences for the basic research and the clinicalprevention and treatment research for lung cancer metastasis.
中图分类号 R734.2 DOI 10.3781/j.issn.1000-7431.2012.03.003
所属栏目 基础研究
基金项目 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)
收稿日期 2011/10/13
修改稿日期 2011/12/19
网络出版日期
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引用该论文: LI Jing,LIN He-chun,ZHANG Fang-lin,YU Jing-xian,SA Bing-qing,LIU Lei,YAN Ming-xia,YAO Ming. Analysis of differentially expressed genes between the high-metastatic and low-metastatic lung cancer cell lines[J]. Tumor, 2012, 32(3): 164～169
李静,林河春,张方淋,于静娴,萨冰清,刘蕾,闫明霞,姚明. 肺癌高转移和低转移细胞株中差异基因的分析[J]. 肿瘤, 2012, 32(3): 164～169
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【3】MOLLOY T, van't VEER L J. Recent advances in metastasis research[J]. Curr Opin Genet Dev, 2008, 18(1):35-41.
【4】LE P U, ANGERS-LOUSTAU A, DE OLIVEIRA R M, et al. DRR drives brain cancer invasion by regulating cytoskeletal-focal adhesion dynamics[J]. Oncogene, 2010, 29(33):4636-4647.
【5】MINN A J, GUPTA G P, SIEGEL P M, et al. Genes that mediate breast cancer metastasis to lung[J]. Nature, 2005, 436(7050):518-524.
【6】BROWN R L, REINKE L M, DAMEROW M S, et al. CD44 splice isoform switching in human and mouse epithelium is essential for epithelial-mesenchymal transition and breast cancer progression[J]. J Clin Invest, 2011, 121(3):1064-1074.
【7】SIMPSON C D, ANYIWE K, SCHIMMER A D. Anoikis resistance and tumor metastasis[J]. Cancer Lett, 2008, 272(2):177-185.
【8】SHI W D, MENG Z Q, CHEN Z, et al. Identification of liver metastasis-related genes in a novel human pancreatic carcinoma cell model by microarray analysis[J]. Cancer Lett, 2009, 283(1):84-91.
【9】JIA D, YAN M X, WANG X, et al. Development of a highly metastatic model that reveals a crucial role of fibronectin in lung cancer cell migration and invasion[J]. BMC Cancer, 2010, 10:364-375.
【10】YANO K, IMAI K, SHIMIZU A, et al. A new method for gene discovery in large-scale microarry data[J]. Nucleic Acids Res, 2006, 34(5):1532-1539.
【11】DUPUV D, BERTIN N, HIDALGO C A, et al. Genome-scale analysis of in vivo spatiotemporal promoter activity in caenorhabditis elegans[J]. Nat Biotechnol, 2007, 25(6):663-668.
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