Figure 3.

Depleting c-MET results in a limited effect of restoring PARPi sensitivity to talazoparib in the PARPi-resistant TNBC cells. (A) Following lentiviral delivery of two independent short hairpin RNAs (shRNA) targeting c-MET to B3 and C12 PARPi-resistant TNBC cells, c-MET expression levels were reduced by at least 50% relative to cells receiving non-specific shRNA sequences. B3 and C12 cells were infected with control shRNA (control), a shRNA targeting the 3’ UTR of c-MET (sh-c-MET-1), or a shRNA targeting the coding region of c-MET (sh-c-MET-2). Relative expression levels of total c-MET in stable clones were determined by immunoblotting. (B) C12 (750) and (C) B3 (1,500) cells were seeded in each well of a 96-well plate on Day 0. On Day 1, talazoparib was added at varying concentrations to each well (12.5-200 nM). Following 6 days of treatment, cells were subjected MTT, and the percentage of surviving cells in each well was calculated. Error bars represent SEM. *P < 0.05, **P < 0.01, ***P < 0.001, Student’s t-test.