title: Biologic roles of estrogen receptor-β and insulin-like growth factor-2 in triple-negative breast cancer.
abstract: Triple-negative breast cancer (TNBC) occurs in 10-15% of patients yet accounts for almost half of all breast cancer deaths. TNBCs lack expression of estrogen and progesterone receptors and HER-2 overexpression and cannot be treated with current targeted therapies. TNBCs often occur in African American and younger women. Although initially responsive to some chemotherapies, TNBCs tend to relapse and metastasize. Thus, it is critical to find new therapeutic targets. A second ER gene product, termed ERβ, in the absence of ERα may be such a target. Using human TNBC specimens with known clinical outcomes to assess ERβ expression, we find that ERβ1 associates with significantly worse 5-year overall survival. Further, a panel of TNBC cell lines exhibit significant levels of ERβ protein. To assess ERβ effects on proliferation, ERβ expression in TNBC cells was silenced using shRNA, resulting in a significant reduction in TNBC proliferation. ERβ-specific antagonists similarly suppressed TNBC growth. Growth-stimulating effects of ERβ may be due in part to downstream actions that promote VEGF, amphiregulin, and Wnt-10b secretion, other factors associated with tumor promotion. In vivo, insulin-like growth factor-2 (IGF-2), along with ERβ1, is significantly expressed in TNBC and stimulates high ERβ mRNA in TNBC cells. This work may help elucidate the interplay of metabolic and growth factors in TNBC.
authors: UCLA School of Nursing, Los Angeles, CA 90095, USA ; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA.
authors: Nalo
authors: 0000-0002-6717-8079
authors: N
authors: Hamilton
authors: UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA ; Division of Hematology-Oncology, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA.
authors: Diana
authors: 0000-0002-4693-3063
authors: D
authors: Márquez-Garbán
authors: UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA ; Department of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA.
authors: Vei
authors: 0000-0003-0186-7805
authors: V
authors: Mah
authors: UCLA School of Nursing, Los Angeles, CA 90095, USA.
authors: Gowry
authors: 0000-0002-7689-2602
authors: G
authors: Fernando
authors: Division of Cancer Research and Training, Department of Medicine, Charles Drew University School of Medicine and Science, Los Angeles, CA 90095, USA.
authors: Yahya
authors: Y
authors: Elshimali
authors: UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA ; Division of Dermatology, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA.
authors: Hermes
authors: H
authors: Garbán
authors: UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA ; Division of General Internal Medicine, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA.
authors: David
authors: D
authors: Elashoff
authors: UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA ; Division of Hematology-Oncology, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA ; Division of Cancer Research and Training, Department of Medicine, Charles Drew University School of Medicine and Science, Los Angeles, CA 90095, USA.
authors: Jaydutt
authors: J
authors: Vadgama
authors: UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA ; Department of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA.
authors: Lee
authors: L
authors: Goodglick
authors: UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA ; Division of Hematology-Oncology, Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA.
authors: Richard
authors: 0000-0002-2846-3192
authors: R
authors: Pietras
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D049109:Cell Proliferation; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D047629:Estrogen Receptor beta; D009363:Neoplasm Proteins; D007335:Insulin-Like Growth Factor II