Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression analysis of 4T1 tumors expressing mouse urokinase plasminogen activitor (uPA)

ABSTRACT: Analysis of uPA regulation of 4T1 tumor growth at gene expression level. The hypothesis tested in the present study was that overexpression of uPA in 4T1 tumor influence the tumor growth and metastasis related cell signaling pathway. 4T1 cells were stably transduced by lentiviral vector expressing mouse uPA or empty vector. After day 7 of inoculation of 4T1 cells into fatpad of Balb/c mice. Total RNA was extracted from tumor samples (triplicate) using Qiagen total RNA isolation kit. The Illumina MouseWG-6 v2.0 Expression BeadChip (Illumina, Wallingford, CT) was used for gene expression. The raw data from the fluorescence intensity measurements of each array experiment was processed using GeneSpringGX v.11.0 software (Agilent, Santa Clara, CA). Statistical analysis, fold change calculations, and hierarchical clustering of the data were also performed in GeneSpring software. Genes that expressed significantly differently with more than 1.5-fold change and a p-value of <0.05 with respect to controls were taken into consideration. Gene expression data were further validated by qRT-PCR analysis. Pathway analysis was performed by MetaCore software (GeneGo, Inc, St. Joseph, MI).

ORGANISM(S): Mus musculus

SUBMITTER: YUQI JING

PROVIDER: E-GEOD-38346 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Data from clinical studies, cell culture, and animal models implicate the urokinase (uPA)/Plasminogen (Plg) system in the development of atherosclerosis and aneurysms. However, the mechanisms through which uPA/Plg stimulate these diseases are not yet defined. We used genetically modified, atherosclerosis-prone mice, including mice with macrophage-specific uPA overexpression to clarify mechanisms of uPA/Plg-accelerated atherosclerosis and aneurysm formation. Microarray studies were performed to identify potential mediators of uPA-accelerated atherosclerosis. These studies identified S100A8 and S100A9 mRNA as the most highly upregulated transcripts in uPA-overexpressing macrophages; upregulation of S100A9 protein in uPA-overexpressing macrophages was confirmed by Western blotting. S100A8/A9, which are atherogenic in mice and are expressed in human atherosclerotic plaques, are also upregulated in aortae of mice with uPA-overexpressing macrophages, and macrophage S100A9 mRNA is upregulated by exposure of wild-type macrophages to medium from uPA-overexpressing macrophages. Bioinformatics analysis of the microarray data suggest significant effects of uPA overexpression on cell migration and cell-matrix interactions. Our results confirm—in a second animal model—that macrophage-expressed uPA stimulates atherosclerosis and aortic dilation. They also implicate specific pathways in uPA/Plg-accelerated atherosclerosis and aneurysmal disease. Six independent biological replicate RNA samples were prepared from thioglycollate-elicited peritoneal macrophages from mice of two different genotypes: SR-uPA+/0 transgenic (overexpress uPA in macrophages) and nontransgenic, respectively), for a total of 12 independent RNA samples. Both transgenic and nontransgenic mice were Apoe-/- and were fed Western diet from 5-15 weeks before peritoneal macrophages were elicited. In addition, from the six samples of each genotype, a pooled sample was prepared by combining the six genotype-specific samples. Each of the two pooled samples was assayed on the BeadChip in two technical replicates, for a total of 16 hybridizations performed using two Illumina Mouse Ref-8 v1.1 chips.

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Gene expression analysis of 4T1 tumors expressing mouse urokinase plasminogen activitor (uPA)

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