Targeting androgen receptor in estrogen receptor-negative breast cancer.
Cancer Cell, 2011/7/12;20(1):119-31.
Ni M[1], Chen Y, Lim E, Wimberly H, Bailey ST, Imai Y, Rimm DL, Liu XS, Brown M
Affiliations
PMID: 21741601DOI: 10.1016/j.ccr.2011.05.026
Impact factor: 38.585
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.
MeSH terms
Androgens; Anilides; Animals; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Dihydrotestosterone; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hepatocyte Nuclear Factor 3-alpha; Humans; Mice; Nitriles; Receptor, ErbB-2; Receptors, Androgen; Receptors, Estrogen; Signal Transduction; Tosyl Compounds; Transcriptional Activation; Up-Regulation; Wnt Proteins; Xenograft Model Antitumor Assays; beta Catenin
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