Fig. 1: Targeting the MAPK pathway is inadequate and compromised by HER2 activation. | Nature Communications

Fig. 1: Targeting the MAPK pathway is inadequate and compromised by HER2 activation.

From: Combined KRAS-MAPK pathway inhibitors and HER2-directed drug conjugate is efficacious in pancreatic cancer

Fig. 1

a Western blots showing dose-dependent increases in phosphorylated ERK1/2, p90RSK, and cleaved caspase-3 levels in PDAC cells treated with the indicated concentrations of gemcitabine for 24 h. b Western blots showing changes in p-ERK1/2, p-AKT(S473), and cleaved caspase-3 levels after treatment with the indicated agents for 24 h. c Correlation plots with Pearson coefficients (R) showing strong positive correlation between MAPK and two independent gemcitabine resistance signatures in PDAC samples from TCGA PanCancer database. d Growth kinetics of subcutaneous Pa01c and Pa02c xenograft tumours treated as indicated when the tumour volume reached ~100 mm3. Data are presented as mean ± SEM. P-values were calculated using two-way ANOVA with Tukey’s multiple comparison test. e Heatmap of RPPA data showing significantly upregulated and downregulated markers in Pa01c and HPAC cells treated with ulixertinib or trametinib for 24 h. f Venn diagram showing the shared changes in both cell lines. Only markers showing a Log2 fold change or <-1 or >1 are illustrated. Data are presented as the mean ± SEM of two biological samples. g Western blots showing changes in p-ERK1/2, DUSP4, and DUSP6 levels in 293 T cells transfected with HER1, HER2, or HER3 for 36 h and then treated with DMSO or afatinib for 16 h. h Western blots showing changes in different phosphorylated-HER2 signals, p-HER3, p-ERK1/2, p-AKT, DUSP4, and DUSP6, in Pa01c and HPAC cells treated with ulixertinib or trametinib for 24 h. a, b, g, h were conducted two times, and one set of data was presented. Source data are provided in Source Data file.

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