SP100 inhibits ETS1 activity in primary endothelial cells

John S. Yordy, Omar Moussa, Huiping Pei, Damien J. Chaussabel, Runzhao Li, Dennis K. Watson

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)916-931
Number of pages16
JournalOncogene
Volume24
Issue number5
DOIs
Publication statusPublished - 27 Jan 2005
Externally publishedYes

Fingerprint

Human Umbilical Vein Endothelial Cells
Endothelial Cells
3-Oxo-5-alpha-Steroid 4-Dehydrogenase
Connective Tissue Growth Factor
Biological Phenomena
Nuclear Antigens
GABA Receptors
Microarray Analysis
Heat-Shock Proteins
Oligonucleotide Array Sequence Analysis
Interferons
Genes
Cell Movement
Real-Time Polymerase Chain Reaction
Transcription Factors
Gene Expression
DNA

Keywords

  • Angiogenesis
  • ETS1
  • Microarray
  • Migration
  • SP100
  • Transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Yordy, J. S., Moussa, O., Pei, H., Chaussabel, D. J., Li, R., & Watson, D. K. (2005). SP100 inhibits ETS1 activity in primary endothelial cells. Oncogene, 24(5), 916-931. https://doi.org/10.1038/sj.onc.1208245

SP100 inhibits ETS1 activity in primary endothelial cells. / Yordy, John S.; Moussa, Omar; Pei, Huiping; Chaussabel, Damien J.; Li, Runzhao; Watson, Dennis K.

In: Oncogene, Vol. 24, No. 5, 27.01.2005, p. 916-931.

Research output: Contribution to journalArticle

Yordy, JS, Moussa, O, Pei, H, Chaussabel, DJ, Li, R & Watson, DK 2005, 'SP100 inhibits ETS1 activity in primary endothelial cells', Oncogene, vol. 24, no. 5, pp. 916-931. https://doi.org/10.1038/sj.onc.1208245
Yordy, John S. ; Moussa, Omar ; Pei, Huiping ; Chaussabel, Damien J. ; Li, Runzhao ; Watson, Dennis K. / SP100 inhibits ETS1 activity in primary endothelial cells. In: Oncogene. 2005 ; Vol. 24, No. 5. pp. 916-931.
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