Figure 6
From: Repression of AKT signaling by ARQ 092 in cells and tissues from patients with Proteus syndrome
High concentrations of ARQ 092 were needed to reduce viability of cells from patients with Proteus syndrome.
ATP levels were measured using a luminescent assay in mutation-positive and mutation-negative SCCs and patient fibroblasts grown in high (10%) or low (0.5%) serum. The percentage of viable cells at a given dose was calculated as described in the Methods. (a) Luminescence ratios of SCCs grown in high or low serum with increasing concentrations of ARQ 092. Clones 1 and 3 are mutation-positive; clones 2 and 4 are mutation-negative. (b) Luminescence ratios of mutation-positive and mutation-negative fibroblasts from patients PS53 and PS75 grown in high or low serum with increasing concentrations of ARQ 092. The level of the AKT1 E17K mutation in cells from patients PS53 and PS75 were 37–42% and zero in the PS53 and PS75 mutation-negative cells. Mutation-positive clones and cells had lower viability and were clearly separated from mutation-negative clones and cells in both high and low serum. At 1.25 uM, levels 10-fold higher than necessary to effectively reduce AKT signaling, 40–70% of cells were still viable. CL1, clone 1; CL2, clone 2; CL3, clone 3; CL4, clone 4; pos, mutation-positive cells; neg, mutation negative cells V-numbers in the legend indicate the experiment number for the data represented by that line.
