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RUNX3 acts as a tumor suppressor in breast cancer by targeting estrogen receptor α

Oncogene volume 31, pages 527–534 (2012)Cite this article

Abstract

Transcription factor RUNX3 is inactivated in a number of malignancies, including breast cancer, and is suggested to function as a tumor suppressor. How RUNX3 functions as a tumor suppressor in breast cancer remains undefined. Here, we show that about 20% of female Runx3+/− mice spontaneously developed ductal carcinoma at an average age of 14.5 months. Additionally, RUNX3 inhibits the estrogen-dependent proliferation and transformation potential of ERα-positive MCF-7 breast cancer cells in liquid culture and in soft agar and suppresses the tumorigenicity of MCF-7 cells in severe combined immunodeficiency mice. Furthermore, RUNX3 inhibits ERα-dependent transactivation by reducing the stability of ERα. Consistent with its ability to regulate the levels of ERα, expression of RUNX3 inversely correlates with the expression of ERα in breast cancer cell lines, human breast cancer tissues and Runx3+/− mouse mammary tumors. By destabilizing ERα, RUNX3 acts as a novel tumor suppressor in breast cancer.

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Acknowledgements

We thank W Xu for reagents; W Xu, A Nardulli and members in the Chen lab for discussion. This work is supported in part by fund provided by UIUC (to LFC) and NIH grants DK-085158 (to LFC), CA116616 (to GTX) and DK-071909 (to DS). YHT is an A*STAR-Illinois Partnership fellow.

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Authors and Affiliations

  1. Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA

    B Huang, Y-H N Tsang, D Shapiro & L-F Chen

  2. University of Pittsburgh Cancer Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Z Qu & G Xiao

  3. Department of Pathology, National University of Singapore, Singapore

    C W Ong & M Salto-Tellez

  4. Cancer Science Institute of Singapore, National University of Singapore, Singapore

    C W Ong, M Salto-Tellez & Y Ito

  5. Institute of Molecular and Cell Biology, Singapore

    Y-H N Tsang & Y Ito

  6. Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

    K Ito

  7. College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA

    L-F Chen

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  1. B Huang
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  2. Z Qu
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  3. C W Ong
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  7. M Salto-Tellez
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  8. K Ito
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Correspondence to K Ito or L-F Chen.

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Huang, B., Qu, Z., Ong, C. et al. RUNX3 acts as a tumor suppressor in breast cancer by targeting estrogen receptor α. Oncogene 31, 527–534 (2012). https://doi.org/10.1038/onc.2011.252

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