Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer

Min Ni, Yiwen Chen, Elgene Lim, Hallie Wimberly, Shannon T. Bailey, Yuuki Imai, David L. Rimm, X. Shirley Liu, Myles Brown

Research output: Contribution to journalArticle

226 Scopus citations

Abstract

Endocrine therapies for breast cancer that target the estrogen receptor (ER) are ineffective in the 25%-30% of cases that are ER negative (ER-). Androgen receptor (AR) is expressed in 60%-70% of breast tumors, independent of ER status. How androgens and AR regulate breast cancer growth remains largely unknown. We find that AR is enriched in ER- breast tumors that overexpress HER2. Through analysis of the AR cistrome and androgen-regulated gene expression in ER-/HER2+ breast cancers we find that AR mediates ligand-dependent activation of Wnt and HER2 signaling pathways through direct transcriptional induction of WNT7B and HER3. Specific targeting of AR, Wnt or HER2 signaling impairs androgen-stimulated tumor cell growth suggesting potential therapeutic approaches for ER-/HER2+ breast cancers.

Original languageEnglish (US)
Pages (from-to)119-131
Number of pages13
JournalCancer Cell
Volume20
Issue number1
DOIs
StatePublished - Jul 12 2011

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Ni, M., Chen, Y., Lim, E., Wimberly, H., Bailey, S. T., Imai, Y., Rimm, D. L., Shirley Liu, X., & Brown, M. (2011). Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer. Cancer Cell, 20(1), 119-131. https://doi.org/10.1016/j.ccr.2011.05.026