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. 2018 Oct 23;38(10):1717–1733. doi: 10.1038/s41388-018-0554-z

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Multiple inflammatory gene expression signatures are enriched in MEK inhibitor-resistant colorectal cancer cell lines. a Differential expression analysis (comparative marker selection, Morpheus, The Broad Institute) of basal gene expression profiles for KRAS-mutant colorectal cancer cell lines identified genes that were differentially overexpressed in cells resistant to the MEK inhibitor PD0325901 (top 50 genes shown). b Box and whisker plots representing the expression of candidate resistance genes in MEK inhibitor-sensitive versus MEK inhibitor-resistant cell lines. Box indicates the 25–75% percentiles and whiskers are the minimum to maximum values. c Gene set enrichment analysis (GSEA) of the rank-ordered, differentially expressed genes in MEK inhibitor-resistant cell lines identified an enrichment of multiple inflammation-related gene sets. d GSEA identified interferon response genes to be significantly enriched in the resistant cell lines (FDR < 0.001, p < 0.001). e Cells were treated with DMSO or 30 nmol/L trametinib for 3 d and cell lysates analyzed by western blotting for the indicated proteins