PI3K Activity Mediates the Epithelial to Mesenchymal Transition Process in MCF10A Cells and Tumor Growth and Metastasis in a Murine Model of Breast Cancer.

Abstract

Breast cancer represents the leading cause of mortality among women worldwide. Triple negative breast cancer (TNBC) subtype does not express estrogen receptor, progesterone receptor and Her2, as well as presents a high expression of Ki67. In addition, TNBC presents the highest incidence of metastasis. Erythropoietin (EPO) is a hematopoietic cytokine that is produced in the kidney; however, EPO is also produced in non-hematopoietic cells. Treatment of breast cancer patients with EPO is associated with poor prognosis and decrease of survival. Epithelial to mesenchymal transition (EMT) is a reversible process in which epithelial cells decrease or lose their epithelial characteristics and acquire properties of mesenchymal cells. EMT is implicated in normal processes and tumor progression. We previously demonstrated that EPO induces an EMT process in MCF10A mammary non-tumorigenic epithelial cells. In this study, we demonstrate that PI3K activity mediates the EMT process induced by EPO in MCF10A cells. Moreover, Balb/cJ mice inoculated with TNBC 4T1 cells and treated with EPO develop mammary tumors with more weight and volume and an increase in the total number of metastatic nodules in lungs and liver through PI3K activity compared with untreated Balb/cJ mice inoculated with 4T1 cells. In conclusion, PI3K activity mediates the EMT process in MCF10A cells and the growth of mammary tumors and metastasis to lungs and liver induced by EPO in Balb/cJ mice inoculated with TNBC 4T1 cells.