Figure 5

Cancer cells harbouring CCNE1 gene amplification show increased sensitivity to CDK2 silencing and chemical inhibition. (A) The fraction of cells in each phase of the cell cycle are shown following transfection with CCNE1 short interfering RNA (siRNA) and control (siCON) in cell lines with (HCC1569 and MDA-MB-157) and without (MDA-MB-231, ZR75.1, BT474 and JIMT1) CCNE1 amplification. (B) Bar plots illustrating the survival fraction of cells following transfection with CDK2 siRNA using individual duplex oligonucelotides (1 to 4) and a SMARTpool (SP) in cancer cells harbouring (red) or lacking (black) 19q12 amplification. Error bars represent the standard error of the mean of three replicates. Survival fractions are shown relative to those of siCON transfected cells. (* depicts significant t-test P values for the comparison of the survival fraction between cells with and without amplification of the target gene for an individual oligonucleotide). (C) Effects on CDK2 protein expression of CDK2 siRNA silencing with Dharmacon individual oligonucelotides and SMARTpool (SP) in MDA-MB-157 cells. (D) Dose response curves of breast cancer cell lines with (red) or without (black) 19q12 amplification to the CDK1, CDK2, and CDK9 inhibitor ADZ5438.