a) Venn diagram describing the intersection of proteins identified by RPPA as differentially regulated in MutL− (intersection of shMLH1, shPMS1 and shPMS2) vs MutL+ (shLuc) MCF7 cells, and genes with significantly dysregulated expression levels in MutL− (shPMS1) vs MutL+ (shLuc) MCF7 cells, after fulvestrant treatment. Inset of pathway based on significantly dysregulated genes identified. All significant protein level and RNA level changes are depicted in Fig S4a+b. b–d) Western blot validation of pChk2, p21 and p27 levels in MCF7 MutL+ (shLuc) and MutL− (shMLH1) cells grown in vitro (b) and in vivo as xenograft tumors (c), and in patient derived MutL− (PMS2 mutant, WHIM20) and MutL+ (WHIM16) xenografts (d), with accompanying quantification. Additional Western blot validation in MCF7 shPMS2 cells and in other PDX tumors in Fig S4c–e. Quantification performed using ImageLab software. Treatment as indicated. For all graphs, columns represent the mean, error bars describe standard deviation and Student’s t-test determined p-values.