Raloxifene reduces triple-negative breast cancer tumor growth and decreases EGFR expression
| Autor: | Rhonda J. Rosengren, Sebastien Taurin, Kirstie M. Allen, Marissa J. Scandlyn |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Carcinogenesis Estrogen receptor Apoptosis Triple Negative Breast Neoplasms Biology Mice Breast cancer Cell Movement Internal medicine medicine Animals Humans Neoplasm Invasiveness Raloxifene Epidermal growth factor receptor Triple-negative breast cancer Cancer medicine.disease ErbB Receptors Gene Expression Regulation Neoplastic Receptors Estrogen Selective estrogen receptor modulator Tumor progression Raloxifene Hydrochloride Cancer research biology.protein medicine.drug |
| Zdroj: | International Journal of Oncology. 43:785-792 |
| ISSN: | 1791-2423 1019-6439 |
| DOI: | 10.3892/ijo.2013.2012 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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