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. Author manuscript; available in PMC: 2015 May 12.
Published in final edited form as: Nat Commun. 2014 Dec 15;5:5712. doi: 10.1038/ncomms6712

Figure 3. MITF loss causes cross-resistance to MAPK pathway inhibition.

Figure 3

(a) Two PLX4720-resistant cell lines (888mel and SkMel28) and their treatment-naïve counterparts were treated with either the ERKi SCH772984 (0.5 μM), the MEKi trametinib (0.3 μM), BRAF inhibitor dabrafenib (3 μM) or a combination as indicated and stained with crystal violet after 6 days of treatment. (b) Immunoblotting for the indicated proteins confirmed the downregulation of the MAPK pathway (as judged by P-ERK) and showed cleaved PARP (arrow) as a measure of apoptosis of the cell lines used in a. CDK4 served as a loading control. (c) Six PLX4720-resistant cell lines and their treatment-naïve counterparts were separated in groups that either lose or maintain (or increase) MITF expression on acquiring resistance. These cells were exposed to the MEKi trametinib or the ERKi SCH772984 in dose–response curves. IC40 (for MEKi) or IC50 (for ERKi) were calculated from the curves. Fold increase in IC40 or IC50 was determined comparing resistant to sensitive cells. Mean was calculated from three independent experiments, error bars indicate s.d.