Figure 2: ATM loss-of-function in lung cancer cell lines triggers MEK inhibitor sensitivity.
From: MEK inhibitors block growth of lung tumours with mutations in ataxia–telangiectasia mutated
(a) Chemical structures of MEK inhibitors used in this study. (b) Dose–response experiment of ATM knockdown (shRNA1) AALE cells infected with the indicated MEK1 expression vectors and treated with trametinib for 3 days. Data are normalized to vehicle-treated cells. Error bars indicate s.d.’s (n=3). (c) Dose–response experiment of ATM knockdown NCI-H322 cells treated with trametinib for 5 days. Data are normalized to vehicle-treated cells. Error bars indicate s.d.’s (n=3). (d) Effective concentration resulting in 50% growth inhibitory effect (EC50) is depicted for indicated cell line and compound combinations. The EC50 for the unresponsive control NCI-H460 cells was set to 20 μM. (e) Western blot analysis of CRISPR/Cas9 edited NCI-H322 clones. (f) Dose–response experiment of NCI-H322 cells in which both ATM alleles have been inactivated (four KO clones) or unedited control (four WT clones) treated with PD0325901, TAK-733, trametinib or pimasertib for 5 days. Data are normalized to vehicle-treated cells. Error bars indicate s.d.’s (n=3).
