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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
10:36

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

Targeting androgen receptor in estrogen receptor-negative breast cancer

Min Ni1, Yiwen Chen, Elgene Lim

  • 1Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.

Cancer Cell
|July 12, 2011
PubMed

Insights

Androgen receptor (AR) drives growth in estrogen receptor-negative, HER2-positive breast cancers by activating Wnt and HER2 pathways. Targeting AR, Wnt, or HER2 offers potential new therapies for this breast cancer subtype.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Estrogen receptor (ER)-targeted therapies are ineffective for 25%-30% of ER-negative breast cancers.
  • Androgen receptor (AR) is present in 60%-70% of breast tumors, irrespective of ER status.
  • The role of androgens and AR in breast cancer progression is not well understood.

Purpose of the Study:

  • To investigate the role of androgen receptor (AR) in ER-negative breast cancers, particularly those overexpressing HER2.
  • To elucidate the molecular mechanisms by which androgens and AR regulate tumor growth in ER-/HER2+ breast cancer.

Main Methods:

  • Analysis of AR enrichment in ER-negative breast tumors.
  • AR cistrome analysis and gene expression profiling in ER-/HER2+ breast cancers.
  • Assessment of tumor cell growth inhibition by targeting AR, Wnt, or HER2 signaling pathways.

Main Results:

  • AR is found to be enriched in ER-negative breast tumors that also overexpress HER2.
  • AR mediates ligand-dependent activation of Wnt and HER2 signaling pathways.
  • AR directly induces the transcription of WNT7B and HER3 genes.

Conclusions:

  • Androgen receptor (AR) signaling plays a critical role in the growth of ER-/HER2+ breast cancers.
  • Targeting AR, Wnt, or HER2 signaling pathways can impair androgen-stimulated tumor growth.
  • These findings suggest novel therapeutic strategies for ER-/HER2+ breast cancers.

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