title: Erythropoietin Induces an Epithelial to Mesenchymal Transition-Like Process in Mammary Epithelial Cells MCF10A.
abstract: Anemia is associated with chemotherapy treatment in cancer patients. Erythropoietin (EPO) has been used to treat anemia of cancer patients, because it stimulates erythropoiesis. However, treatment of breast cancer patients with EPO has been associated with poor prognosis and decrease of survival. Epithelial to mesenchymal transition (EMT) is a process by which epithelial cells are transdifferentiated to a mesenchymal state. It has been implicated in tumor progression, because epithelial cells acquire the capacity to execute the multiple steps of invasion/metastasis process. However, the role of EPO on EMT process in human mammary epithelial cells has not been studied. In the present study, we demonstrate that EPO promotes a decrease of E-cadherin expression, an increase of N-cadherin, vimentin, and Snail2 expression, activation of FAK and Src kinases and an increase of MMP-2 and MMP-9 secretions. Moreover, EPO induces an increase of NFκB DNA binding activity, an increase of binding of p50 and p65 NFκB subunits to Snail1 promoter, migration, and invasion in mammary non-tumorigenic epithelial cells MCF10A. In summary, these findings demonstrate, for the first time, that EPO induces an EMT-like process in mammary non-tumorigenic epithelial cells. J. Cell. Biochem. 118: 2983-2992, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Departamento de Biología Celular, Cinvestav-IPN, Av. IPN # 2508, San Pedro Zacatenco, Mexico.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ordoñez-Moreno
authors.affiliation: Departamento de Biología Celular, Cinvestav-IPN, Av. IPN # 2508, San Pedro Zacatenco, Mexico.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rodriguez-Monterrosas
authors.affiliation: Departamento de Biología Celular, Cinvestav-IPN, Av. IPN # 2508, San Pedro Zacatenco, Mexico.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cortes-Reynosa
authors.affiliation: Instituto Nacional de Medicina Genomica, Periferico Sur 4214, Ciudad de Mexico, Mexico.
authors.forename: Julio Isael
authors.initials: JI
authors.lastname: Perez-Carreon
authors.affiliation: Departamento de Biología Celular, Cinvestav-IPN, Av. IPN # 2508, San Pedro Zacatenco, Mexico.
authors.forename: Eduardo
authors.identifier: 0000-0002-3041-7902
authors.initials: E
authors.lastname: Perez Salazar
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D004921:Erythropoietin / Q000378:metabolism*; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*
chemical_list: C554270:EPO protein, human; D009363:Neoplasm Proteins; D004921:Erythropoietin
keywords: BREAST CANCER; EMT; ERYTHROPOIETIN; INVASION; MCF10A