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The Ets protein PEA3 suppresses HER-2/neu overexpression and inhibits tumorigenesis

Nature Medicine volume 6, pages 189–195 (2000)Cite this article

Abstract

Because HER-2/neu overexpression is important in cancer development, we looked for a method of suppressing the cell transformation mediated by HER-2/neu overexpression. We have identified that the DNA-binding protein PEA3, which is encoded by a previously isolated gene of the ets family, specifically targeted a DNA sequence on the HER-2/neu promoter and downregulated the promoter activity. Expression of PEA3 resulted in preferential inhibition of cell growth and tumor development of HER-2/neu-overexpressing cancer cells. This is a new approach to targeting HER-2/neu overexpression and also provides a rationale to the design for repressors of diseases caused by overexpression of pathogenic genes.

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Figure 1: PEA3 binds to the HER-2/neu promoter.
Figure 2: PEA3 inhibits the HER-2/neu promoter activity in HER-2/neu-overexpressing cancer cell lines.
Figure 3: PEA3 represses HER-2/neu promoter activity through a positive regulatory DNA motif.
Figure 4: PEA3 suppresses cell growth and transformation induced by HER-2/neu overexpression.
Figure 5: PEA3 inhibits HER-2/neu-overexpression in vivo.
Figure 6: PEA3 suppresses tumor growth of HER-2/neu-overexpressing cancer cells.

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Acknowledgements

The authors thank J. H. Chen for providing PEA3 cDNA. This work was partially supported by National Institute of Health (NIH) grants (to M.-C. H. and L.H.), M. D. Anderson Breast Cancer Research Program, as well as a NIH cancer center core grant and Biocyte Therapeutics, Inc.. X.X. is the recipient of a predoctoral fellowship from the Breast Cancer Research Program of the Department of Defense, and Z.Y. is a predoctoral fellow under the US Army Breast Cancer Research Training Grant.

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  1. Xiangming Xing and Shao-Chun Wang: X.X. and S.-C.W. equally contributed to this study.

Authors and Affiliations

  1. Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Section of Molecular Cell Biology, Houston, 77030, Texas, USA

    Xiangming Xing, Shao-Chun Wang, Weiya Xia, Yiyu Zou, Ruping Shao, Ka Yin Kwong, Zhenming Yu, Su Zhang, Susan Miller & Mien-Chie Hung

  2. Department of Pharmacology, University of Pittsburgh, Pittsburgh, 15261, Pennsylvania, USA

    Leaf Huang

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Xing, X., Wang, SC., Xia, W. et al. The Ets protein PEA3 suppresses HER-2/neu overexpression and inhibits tumorigenesis. Nat Med 6, 189–195 (2000). https://doi.org/10.1038/72294

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