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  • Original Paper
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SP100 expression modulates ETS1 transcriptional activity and inhibits cell invasion

Oncogene volume 23, pages 6654–6665 (2004)Cite this article

Abstract

The ETS1 transcription factor is a member of the Ets family of conserved sequence-specific DNA-binding proteins. ETS1 has been shown to play important roles in various cellular processes such as proliferation, differentiation, lymphoid development, motility, invasion and angiogenesis. These diverse roles of ETS1 are likely to be dependent on specific protein interactions. To identify proteins that interact with ETS1, a yeast two-hybrid screen was conducted. Here, we describe the functional interaction between SP100 and ETS1. SP100 protein interacts with ETS1 both in vitro and in vivo. SP100 is localized to nuclear bodies and ETS1 expression alters the nuclear body morphology in living cells. SP100 negatively modulates ETS1 transcriptional activation of the MMP1 and uPA promoters in a dose-dependent manner, decreases the expression of these endogenous genes, and reduces ETS1 DNA binding. Expression of SP100 inhibits the invasion of breast cancer cells and is induced by Interferon-α, which has been shown to inhibit the invasion of cancer cells. These data demonstrate that SP100 modulates ETS1-dependent biological processes.

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Acknowledgements

We thank Dr R Brent (The Molecular Sciences Institute, Berkeley, CA) for providing the yeast two-hybrid reagents, Dr R Tjian (University of California, Berkeley) for the pCMV-c-fos and pCMV-c-jun plasmid, Drs J Rutter and C Brinckerhoff (Dartmouth Medical School, NH) for the pGL3-MMP1-2G and pGL3-MMP1-1G plasmids, and Dr Andrew CB Cato for the MMP1-517/+63 luciferase plasmid. This work was supported in part by grants from the National Institutes of Health Grant P01CA78582 (DKW) and American Cancer Society Grant IRG97-151 (RL), as by the Wachovia Hollings Cancer Center scholarship and a Cato scholarship (JSY).

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Author notes

  1. Victor I Sementchenko

    Present address: Affymetrix, Inc., 3380 Central Expressway, Santa Clara, CA, 95051, USA

Authors and Affiliations

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

    John S Yordy, Runzhao Li, Victor I Sementchenko & Dennis K Watson

  2. Department of Medicine, Medical University of South Carolina, Charleston, 29425, SC, USA

    Huiping Pei

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

    Huiping Pei

  4. Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, 29425, SC, USA

    Robin C Muise-Helmericks

  5. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, 29425, SC, USA

    Dennis K Watson

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Correspondence to Dennis K Watson.

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Yordy, J., Li, R., Sementchenko, V. et al. SP100 expression modulates ETS1 transcriptional activity and inhibits cell invasion. Oncogene 23, 6654–6665 (2004). https://doi.org/10.1038/sj.onc.1207891

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