Figure 3.
Effect of small molecule MEK and/or PI3K inhibitors on signaling pathways in GNAQ mutant versus wild-type uveal melanoma. A, Mutant GNAQ [Q209L (92.1, MEL202)] or wild-type (MEL285, MEL290) uveal melanoma cells were treated with MEKi alone (10nM), PI3Ki alone (100nM), or the combination of MEKi + PI3Ki for 4, 12 or 24 hrs. Reverse Phase Protein Array was performed to assess the expression of proteins in the MEK/MAPK, PI3K/AKT, cell cycle and apoptosis pathways. The heatmap represents the mean centered log2 expression value for each protein after the indicated time of treatment (red = greater, green = lesser). Each treatment was performed in triplicate; therefore there are three distinct heatmap boxes per treatment condition. B, The highest scoring network interactions (edge flux values) from the NetWalk analysis of directly measured proteins following 4 hours of MEKi and/or PI3Ki treatment. Nodes represent proteins, edges represent network interactions among nodes, node-coloring represents relative increase in protein level. Asterisks (*) indicate phosphorylated proteins.