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.
OBJECTIVE
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.


CONCLUSIONS
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.
Tianjin Medical University General Hospital, Heping District, Tianjin, China. zhouqh1016@yahoo.com.cn
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D015153:Blotting, Western / Q000379:methods; D018287:Carcinoma, Large Cell / Q000235:genetics* / Q000556:secondary*; D045744:Cell Line, Tumor; D015226:Dinucleoside Phosphates / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D053511:Matrix Metalloproteinase 14 / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics
C527276:CXCR4 protein, human; D015226:Dinucleoside Phosphates; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human; C009628:uridylyl-(3'-5')-adenosine; D053511:Matrix Metalloproteinase 14