Fig. 6

Acquired resistance to BRAF/MEK inhibition associated with de-differentiated phenotype, and not dependent on PI3K or AKT3 transgene expression. Melanoma cells transduced with vector (Control), tetracycline-inducible PIK3CAH1047R (Parent) were compared with the resistant sublines (CR1, CR3), derived after long-term exposure to combination dabrafenib/trametinib. Western blots of lysates showing protein markers of differentiation (MITF, SOX10), MAPK and PI3K/AKT signalling 24 h after treating (a) SKMel28 or (b) MM200 cells with dabrafenib (Dab) and trametinib (Tram) and/or tetracycline (Tet) to induce PIK3CAH1047R expression