Figure 5.
PARP inhibitor sensitivity of cells with mutant EGFR. A, Left panel, Representative images of subnuclear GFP signal (green) overlaid with DAPI (blue) in an isogenic MEF pair with wild-type (wt) or mutant (mut) EGFR transfected with GFP-tagged FAN1. Cells were treated with 10 μM olaparib for 24 hours. Right panel, Fraction of cells with ≥ 5 FAN1 foci. B, RAD51 foci formation in cell lines as indicated, treated with 10 μM olaparib for 24 or 34 hours. C, Clonogenic survival of lung cancer and NIH3T3 cell lines after treatment with olaparib for 72 hours. Estimated IC50 values for each cell line are indicated. D, Left panel, Representative images of γ-H2AX signal in cell lines treated with olaparib for 24 hours. Right upper panel, Representative nucleus after counterstaining tumor tissue derived from a lung cancer patient with DAPI (blue), PCNA (red), and γ-H2AX (green). Right lower panel, Fraction of PCNA-positive nuclei containing γ-H2AX foci following ex-vivo treatment of EGFR mutant versus wild-type tumor tissue with 10 μM olaparib for 24 hours. All data represent mean ± standard error based on 2-5 biological repeats, except in D bars represent average number of positive nuclei ± 95% confidence intervals.