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

B Huang, Z Qu, C W Ong, Y-H N Tsang, G Xiao, D Shapiro, M Salto-Tellez, K Ito, Y Ito, L-F Chen

Research output: Contribution to journalArticle

50 Citations (Scopus)

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 ERa-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 ERa-dependent transactivation by reducing the stability of ERa. Consistent with its ability to regulate the levels of ERa, expression of RUNX3 inversely correlates with the expression of ERa in breast cancer cell lines, human breast cancer tissues and Runx3(+/-) mouse mammary tumors. By destabilizing ERa, RUNX3 acts as a novel tumor suppressor in breast cancer.
Original languageEnglish
Pages (from-to)527-34
Number of pages8
JournalOncogene
Volume31
Issue number4
DOIs
Publication statusPublished - 26 Jan 2012

Keywords

  • Animals
  • Humans
  • Proteasome Endopeptidase Complex
  • Estrogen Receptor alpha
  • Ubiquitination
  • Core Binding Factor Alpha 3 Subunit
  • Transcription, Genetic
  • Mice
  • Mammary Neoplasms, Experimental
  • Cell Line, Tumor
  • Female
  • Tumor Suppressor Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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  • Cite this

    Huang, B., Qu, Z., Ong, C. W., Tsang, Y-H. N., Xiao, G., Shapiro, D., Salto-Tellez, M., Ito, K., Ito, Y., & Chen, L-F. (2012). RUNX3 acts as a tumor suppressor in breast cancer by targeting estrogen receptor α. Oncogene, 31(4), 527-34. https://doi.org/10.1038/onc.2011.252