IL-1β induces up-regulation of BIRC3, a gene involved in chemoresistance to doxorubicin in breast cancer cells. (1st April 2017)

• Record Type: Journal Article
• Authors: Mendoza-Rodríguez, Mónica; Arévalo Romero, Haruki; Fuentes-Pananá, Ezequiel M.; Ayala-Sumuano, Jorge-Tonatiuh; Meza, Isaura
• Is Part Of: Cancer letters. Volume 390(2017)
• Page Start: 39
• Page End: 44
• Publication Date: 2017-04-01
• Subjects: IL-1β stimulation -- Drug sensitivity -- Cell survival genes; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2017.01.005
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Epithelial to mesenchymal transition (EMT) of tumor cells facilitates their progress to metastasis. In the tumor microenvironment the inflammatory cytokine 1β (IL-1β) has been associated with tumor development and invasiveness. IL-1β-induced EMT triggers the expression of markers associated with malignancy. We have recently reported that an IL-1β-highly responsive clone (6D cells) from non-invasive MCF-7 breast cancer cells activates PI3K/Rac and IL-1RI/β-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-1β stimulation of 6D cells. The expression of CDKN1A, TP63, SFN and, particularly, BIRC3 was found to be up-regulated in a RNA-seq analysis and validated by qPCR. Cells stimulated with IL-1β when challenged with doxorubicin showed resistance to the drug, whereas silencing of BIRC3 decreased viability of the cells treated with the drug. Our present results show that IL-1β confers doxorubicin resistance to breast cancer cells, underlining the importance of an inflammatory environment in cancer malignancy. Highlights: IL-1β induces over expression of cell survival genes. The up-regulated genes were identified by RNA-seq analysis. CDKN1A, TP63 and BIRC3 were the significantly up-regulated genes. BIRC3 participates in resistance to doxorubicin. IL-1β-induced EMT is correlated with chemoresistance to doxorubicin.