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  • Original Paper
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SP100 inhibits ETS1 activity in primary endothelial cells

Oncogene volume 24, pages 916–931 (2005)Cite this article

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.

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Acknowledgements

We thank Joan Hebert from the Stanford Functional Genomics Facility for help in obtaining the microarrays and annotated files, and Nicki Chin from the Stanford Functional Genomics Facility and Roger Wagner from the Stanford Division of Cardiovascular Medicine, Falk Cardiovascular Research Center for assistance with microarray protocols. We thank Jordan Blessing from ScopeTronix for customizing the adapter used for the afocal microscopy, and Tom Bullington and Chuck Westfall from Canon USA for help in initially testing the digital SLR Canon cameras. This work was supported in part by grants from the National Institutes of Health Grant P01CA78582 and MUSC Institutional Research Funds of 2003–04 (DKW) and by the Wachovia Hollings Cancer Center scholarship and a Cato scholarship (JSY).

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  1. Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA

    John S Yordy, Omar Moussa, Runzhao Li & Dennis K Watson

  2. Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA

    Dennis K Watson

  3. Department of Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA

    Huiping Pei

  4. Baylor Institute for Immunology Research, Dallas, TX, USA

    Damien Chaussabel

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Yordy, J., Moussa, O., Pei, H. et al. SP100 inhibits ETS1 activity in primary endothelial cells. Oncogene 24, 916–931 (2005). https://doi.org/10.1038/sj.onc.1208245

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