Fig. 4
Comparison of the transcriptomic effects of vemurafenib on HDF and BRAFWT melanoma cells. Western blot showing the effect of vemurafenib (PLX) over MEK1/2 and ERK1/2 phosphorylation in A HDF, B SBcl2, and C WM3438 cell lines, after 4 h of stimulation with increasing concentrations of the inhibitor. The phosphorylated (p-) and total proteins are shown. GAPDH served as a loading control. D Gene set enrichment of the MEK-dependent transcriptional signature [57] in BRAFWT melanoma cell lines for the indicated stimulation time-points with 2 µM of vemurafenib. The significance cutoff (q < 0.05) is shown as a dashed red line. E Correlation matrix of the FC after vemurafenib treatment in BRAFWT (HDF, SBcl2, and WM3438) and BRAFV600E positive (MaMel21 and MaMel63a) cell lines, for the subsets of DEGs (p < 0.1) in common for all conditions (n = 33). The correlation level is annotated and represented by the colorimetric scale. Only significant correlations (p < 0.05) are colored. The stimulation time is indicated in parenthesis. F Venn diagram showing the number of DEGs (q < 0.05) on BRAFWT cell lines after 18 h of treatment with 2 µM of vemurafenib. G Heatmap displaying the genes with a paradoxical expression change, consistent in all assayed cell lines. Fold change values of vemurafenib-treated cells with respect to DMSO control are depicted by a colorimetric scale (red: up-regulated, blue: down-regulated)