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. Author manuscript; available in PMC: 2016 Jul 18.
Published in final edited form as: Nat Med. 2016 Jan 18;22(2):194–201. doi: 10.1038/nm.4032

Figure 2. c-Met regulates resistance to PARP inhibitors.

Figure 2

(a) Left, c-Met-knockdown cells were treated with the indicated concentrations of ABT-888 for 72 h and subjected to a cell viability assay. Right, Western blot showing c-Met expression in c-Met-knockdown MDA-MB-231 cells. (b) MDA-MB-231 cells were treated with the indicated concentrations of AG014699 and crizotinib or foretinib for 8 days and subjected to clonogenic cell survival assay. Quantitation of clonogenic cells from three independent experiments is shown. (c) Left, c-Met-knockdown MDA-MB-231 cells were treated with the indicated concentrations of AG014699 for 8 days and subjected to clonogenic cell survival assay. Quantitation of clonogenic cell from three independent experiments is shown. Right, Western blot showing c-Met expression in c-Met- knockdown cells at the 3′-UTR (shMet-C) and re-expression of wild-type (Wt) and kinase dead (KD) c-Met in MDA-MB-231 cells. (d) Western blot analysis of c-Met expression in MCF-7 cells. (e) MCF-7-c-Met and vector control cells were treated with the indicated concentrations of AG014699 for 8 days and subjected to clonogenic cell survival assay. Quantitation of clonogenic cells from three independent experiments is shown. (f) Median inhibitory concentration (IC50) of PARP inhibitors in BRAC1-mutant TNBC cells (MDA-MB-436 and HCC1937). Top, Western blot showing c-Met expression. (g) c-Met-knockdown HCC1937 cells were treated with the indicated concentrations of AG014699 for 72 h and subjected to cell viability assay. Top, Western blot showing c-Met expression in c-Met-knockdown HCC1937 cells. (h) MDA-MB-436 cells with ectopic expression of c-Met were treated with the indicated concentrations of AG014699 for 72 h and subjected to cell viability assay. Top, expression of wild-type (Wt) and kinase dead (KD) c-Met in MDA-MB-436 cells. (i) Western blot showing expression of c-Met in MDA-MB-231 and MDA-MB-157 cells. (j) BRCA1- and BRCA2-knockdown MDA-MB-157 cells were treated with the indicated concentrations of AG014699 for 72 h and subjected to cell viability assay. Right, Western blot showing c-Met expression in c-Met-knockdown MDA-MB-157 cells. Error bars represent s.d. Cri, crizotinib; Ft, foretinib; ABT, ABT-888; AG, AG014699; AZD, AZD2281. *P < 0.05, rANOVA.