title: Targeting androgen receptor in estrogen receptor-negative breast cancer.
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.
authors: Division 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.
authors: Min
authors: M
authors: Ni
authors: Yiwen
authors: Y
authors: Chen
authors: Elgene
authors: E
authors: Lim
authors: Hallie
authors: H
authors: Wimberly
authors: Shannon T
authors: ST
authors: Bailey
authors: Yuuki
authors: Y
authors: Imai
authors: David L
authors: DL
authors: Rimm
authors: X Shirley
authors: XS
authors: Liu
authors: Myles
authors: M
authors: Brown
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000378:metabolism; D006801:Humans; D051379:Mice; D009570:Nitriles / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014105:Tosyl Compounds / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000728:Androgens; D000813:Anilides; D013196:Dihydrotestosterone; D051541:Hepatocyte Nuclear Factor 3-alpha; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D014105:Tosyl Compounds; D051153:Wnt Proteins; D051176:beta Catenin; C410798:AR protein, human; C496499:FOXA1 protein, human; C053541:bicalutamide; C508053:ERBB2 protein, human