IL-1β induces up-regulation of BIRC3, a gene involved in chemoresistance to doxorubicin in breast cancer cells

Epithelial to mesenchymal transition (EMT) of tumor cells facilitates their progress to metastasis. In the tumor microenvironment the inflammatory cytokine 1 beta (IL-1 beta) has been associated with tumor development and invasiveness. IL-1 beta-induced EMT triggers the expression of markers associated with malignancy. We have recently reported that an IL-1 beta-highly responsive clone (6D cells) from noninvasive MCF-7 breast cancer cells activates PI3K/Rac and IL-1RI/beta-catenin pathways that up-regulate the transcription of genes involved in an EMT-like process. However, a correlation between the EMT program induced by a pro-inflammatory environment, and the acquisition of chemoresistance has not been yet determined in these cells. In this work, we report the expression of cell survival genes after IL-1 beta stimulation of 6D cells. The expression of CDKNIA, TP63, SFN and, particularly, BIRC3 was found to be up-regulated in a RNA-seq analysis and validated by qPCR. Cells stimulated with IL-1 beta when challenged with doxorubicin showed resistance to the drug, whereas silencing of BIRD decreased viability of the cells treated with the drug. Our present results show that IL-1 beta confers doxorubicin resistance to breast cancer cells, underlining the importance of an inflammatory environment in cancer malignancy. (C) 2017 Elsevier B.V. All rights reserved.