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The EGF receptor confers BRAF inhibitor resistance in BRAF-mutant melanoma cells. The EGF receptor confers BRAF inhibitor resistance in BRAF-mutant melanoma.

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Presentation on theme: "The EGF receptor confers BRAF inhibitor resistance in BRAF-mutant melanoma cells. The EGF receptor confers BRAF inhibitor resistance in BRAF-mutant melanoma."— Presentation transcript:

1 The EGF receptor confers BRAF inhibitor resistance in BRAF-mutant melanoma cells.
The EGF receptor confers BRAF inhibitor resistance in BRAF-mutant melanoma cells. A–C, proliferation of A375 and A375/R cells (A), Colo829 and Colo829/R cells (B), and A375(X) and A375(X)/R cells (C) in the presence of PLX4720 (PLX). Values are relative to dimethyl sulfoxide (DMSO) controls and IC50 values are mean (μmol/L; n = 3) ± SEM (34). D, Western blot analyses for phosphorylated ERK (pERK) and ERK2 (loading control) in A375, A375/R, A375(X), A375(X)/R, Colo829, and Colo829/R cells in the absence (−) or presence (+) of PLX4720 (2 μmol/L; 24-hour continuous exposure). E, phospho-protein array for A375, A375/R, A375(X), A375(X)/R, Colo829, and Colo829/R cells. VEGFR, VEGF receptor. F, Western blots for phosphorylated EGFR (pEGFR), EGFR, phosphorylated AKT (pAKT), AKT, and tubulin (loading control) in A375, A375/R, A375(X), A375(X)/R, Colo829, and Colo829/R cells. G, graph showing secretion of EGF from sensitive and resistant cells. For each cell pair, data are presented relative to the parental (sensitive) line and are representative of 3 independent experiments with error bars to indicate SE (**, P < 0.01). H, Western blot analysis showing p-Ser-MIG6 in sensitive and resistant cells. The graph below shows quantification (% relative to parental lines) of the Western blots by optical density. Similar results were obtained in 2 independent experiments. I, proliferation of A375, A375/R, A375(X), A375(X)/R, Colo829, and Colo829/R cells in the presence of DMSO, PLX4720 (PLX; 5 μmol/L), or gefitinib (GEF; 2.5 μmol/L). Photographs of fixed cells are positioned with graphs to show quantification. Graphical data are representative of 3 independent experiments with error bars to indicate SE. **, P < 0.01; ***, P < J, growth of A375(X)/R cells as tumor xenografts in nude mice treated with vehicle, PLX4720 (25 mg/kg/d orally), or gefitinib (50 mg/kg/d orally). Drug treatments commenced when tumors reached 40 to 50 mm3 and mean tumor volumes ± SEM (34) are shown (n = 6 mice per group). Maria R. Girotti et al. Cancer Discovery 2013;3: ©2013 by American Association for Cancer Research

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