Systematic name M1211
Brief description Genes up-regulated in HUVEC cells (endothelium) by ETS1 [GeneID=2113] which were down-regulated by SP100 [GeneID=6672].
Full description or abstract SP100 was first identified as a nuclear autoimmune antigen and is a constituent of the nuclear body. SP100 interacts with the ETS1 transcription factor, and we have previously shown that SP100 reduces ETS1-DNA binding and inhibits ETS1 transcriptional activity on the MMP1 and uPA promoters. We now demonstrate that SP100 expression is upregulated by interferons, which have been shown to be antiangiogenic, in primary endothelial cells. As ETS1 is functionally important in promoting angiogenesis, we tested the hypothesis that ETS1 activity is negatively modulated by SP100 in endothelial cells. SP100 directly antagonizes ETS1-mediated morphological changes in human umbilical vein endothelial cell (HUVEC) network formation and reduces HUVEC migration and invasion. To further understand the functional relationship between ETS1 and SP100, cDNA microarray analysis was utilized to assess reprogramming of gene expression by ETS1 and SP100. A subset of the differentially regulated genes, including heat-shock proteins (HSPs) H11, HSPA1L, HSPA6, HSPA8, HSPE1 and AXIN1, BRCA1, CD14, CTGF (connective tissue growth factor), GABRE (gamma-aminobutyric acid A receptor epsilon), ICAM1, SNAI1, SRD5A1 (steroid-5-alpha-reductase 1) and THY1, were validated by real-time PCR and a majority showed reciprocal expression in response to ETS1 and SP100. Interestingly, genes that are negatively regulated by ETS1 and upregulated by SP100 have antimigratory or antiangiogenic properties. Collectively, these data indicate that SP100 negatively modulates ETS1-dependent downstream biological processes.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 15592518   Authors: Yordy JS,Moussa O,Pei H,Chaussabel D,Li R,Watson DK
Exact source Table 2S: [GFP+VEGF vs. SP100/GFP+VEGF] < 0
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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Version history 3.1: First introduced

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