IL-1β induces up-regulation of BIRC3, a gene involved in chemoresistance to doxorubicin in breast cancer cells
IL-1β induces up-regulation of BIRC3, a gene involved in chemoresistance to doxorubicin in breast cancer cells
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DOI：
10.1016/j.canlet.2017.01.005
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发表时间：
2017-04-01
期刊：
影响因子：
9.7
通讯作者：
Meza, Isaura
中科院分区：
文献类型：
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作者：
Mendoza-Rodriguez, Monica;Arevalo Romero, Haruki;Meza, Isaura
肿瘤细胞的上皮间质转化（EMT）促进其向转移的进展。在肿瘤微环境中，炎性细胞因子1 β（IL-1 β）与肿瘤的发展和侵袭性有关。IL-1 β诱导的EMT触发与恶性肿瘤相关的标志物的表达。我们最近报道，来自非侵袭性MCF-7乳腺癌细胞的IL-1 β高反应性克隆（6D细胞）激活PI 3 K/Rac和IL-1 RI/β-连环蛋白通路，这些通路上调参与EMT样过程的基因的转录。然而，在这些细胞中，由促炎环境诱导的EMT程序与获得化学抗性之间的相关性尚未确定。在这项工作中，我们报告了IL-1 β刺激6D细胞后细胞生存基因的表达。在RNA-seq分析中发现CDKN 1A、TP 63、SFN和特别是BIRC 3的表达上调，并通过qPCR验证。当用阿霉素攻击时，用IL-1 β刺激的细胞显示出对药物的抗性，而BIRD的沉默降低了用药物处理的细胞的活力。我们目前的研究结果表明，IL-1 β赋予乳腺癌细胞多柔比星耐药性，强调了炎症环境在癌症恶性肿瘤中的重要性。(C)2017爱思唯尔B. V.保留所有权利。
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.