title: Raloxifene reduces triple-negative breast cancer tumor growth and decreases EGFR expression.
abstract: The poor prognosis of patients with triple-negative breast cancer (TNBC) and the lack of targeted treatments have raised the need for alternative therapies. Previous studies have suggested an effect of raloxifene, a selective estrogen receptor modulator that is independent of the estrogen receptor (ER). Therefore, we assessed the therapeutic value of raloxifene in TNBC mouse models. Mice received a daily oral treatment with different doses of raloxifene. Tumor progression was monitored weekly; in addition microvessel density, proliferation, migration and invasion, apoptosis and tumorigenicity were analyzed. This study demonstrates that raloxifene (0.85 mg/kg) prevents TNBC tumor growth and induces tumor regression. The treated tumors showed a 54% decreased microvascular density and proliferation and a 7-fold increase in apoptosis. The underlying therapeutic mechanism of raloxifene was associated with a 27-fold decrease in the expression of the epidermal growth factor receptor (EGFR). Moreover, raloxifene promoted the translocation of EGFR into endosomes associated with decreased cell migration, cell invasion and tumorigenicity in vitro. Together, these data showed that raloxifene acts independently of the ER and may be relevant for the treatment as well as control the progression of TNBC.
authors.affiliation: Department of Pharmacology and Toxicology, University of Otago, Adams Building, Dunedin 9016, New Zealand.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Taurin
authors.forename: Kirstie M
authors.initials: KM
authors.lastname: Allen
authors.forename: Marissa J
authors.initials: MJ
authors.lastname: Scandlyn
authors.forename: Rhonda J
authors.initials: RJ
authors.lastname: Rosengren
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage*; D011960:Receptors, Estrogen / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics
chemical_list: D011960:Receptors, Estrogen; D020849:Raloxifene Hydrochloride; C541485:EGFR protein, mouse; D066246:ErbB Receptors