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应用 DNA 微阵列技术鉴定与人类大细胞肺癌转移增强相关的 Wnt 通路、uPA、PAI-1、MT1-MMP、S100A4 和 CXCR4。

Identification of Wnt pathway, uPA, PAI-1, MT1-MMP, S100A4 and CXCR4 associated with enhanced metastasis of human large cell lung cancer by DNA microarray.

机构信息

Tianjin Medical University General Hospital, Heping District, Tianjin, China.

出版信息

Minerva Med. 2012 Jun;103(3):151-64.

Abstract

AIM

The aim of this paper was to investigate the differentially expressed genes in large cell lung cancer cell lines with different metastatic potential, and to screen out new candidate genes related to metastasis of lung cancer.

METHODS

The total RNAs of low and high metastatic large cell lung cancer cell lines (NL9980 and L9981) were extracted and processed, then hybridized to Affymetrix HG U133 Plus 2.0 array. The hybridization signals were scanned and compared to find out the differentially expressed genes. Chosen genes were verified by Western Blot. Bioinformatics were used to analyze the functions and related pathways of the genes.

RESULTS

There were 933 differentially expressed genes between NL9980 and L9981 cell lines. In the high metastatic cell line L9981, 672 genes were up-regulated and 260 genes were down-regulated compared with the low metastatic cell line NL9980. The differentially expressed genes were mainly associated with binding, catalytic activity, signal transducer activity and transporter activity, and mainly involved in pathways including, pathways in cancer, focal adhesion, regulation of actin cytoskeleton, ECM-receptor interaction.

CONCLUSION

Differentially expressed genes with the functions including binding, catalytic activity, signal transducer activity and transporter activity may promote metastasis of lung cancer cells through complicated networks including Wnt pathway and metastasis-related genes such as uPA, PAI-1, MT1-MMP, S100A4 and CXCR4.

摘要

目的

本研究旨在探讨不同转移潜能的大细胞肺癌细胞系中差异表达的基因,筛选出与肺癌转移相关的新候选基因。

方法

提取低转移和高转移大细胞肺癌细胞系(NL9980 和 L9981)的总 RNA,进行杂交处理,然后与 Affymetrix HG U133 Plus 2.0 芯片杂交。扫描杂交信号,比较差异表达基因。选择基因用 Western Blot 进行验证。利用生物信息学分析基因的功能和相关通路。

结果

NL9980 和 L9981 细胞系之间有 933 个差异表达基因。在高转移细胞系 L9981 中,与低转移细胞系 NL9980 相比,有 672 个基因上调,260 个基因下调。差异表达基因主要与结合、催化活性、信号转导活性和转运体活性有关,主要涉及癌症通路、黏附斑、肌动蛋白细胞骨架调节、细胞外基质-受体相互作用等通路。

结论

具有结合、催化活性、信号转导活性和转运体活性等功能的差异表达基因可能通过 Wnt 通路等复杂网络,以及 uPA、PAI-1、MT1-MMP、S100A4 和 CXCR4 等转移相关基因促进肺癌细胞的转移。

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