Figure 4.

Elevated MYC expression sensitizes triple-negative cancers to CDK inhibition. (A) A panel of triple-negative as well as receptor-positive breast cells, together with a matched pair of nontumorigenic model epithelial cells (RPE cells) engineered to overexpress MYC, was treated with CDK inhibitors purvalanol A (10 µM) or dinaciclib (10 nM) for 72 h and subjected to viability assay. The dashed line indicates the relative starting cell number at the time of adding CDK inhibitors (time 0). Positive numbers indicate cell growth and negative numbers indicate cell death. The experiment was independently repeated five times. The error bars represent means ± SEM. P-values were calculated by two-tailed Student’s t test for comparisons of cell lines treated with each of the two inhibitors. Western blots showing MYC and actin protein expression from the indicated cell lines are shown. (B) Cell cycle profiles of three triple-negative cell lines and three receptor-positive cell lines after treatment with 10 µM purvalanol A or 10 nM dinaciclib for 72 h. The percentage of cells in G1 and G2-M phases of the cell cycle, as determined by DNA content based on propidium iodide staining, is indicated. (C) A panel of triple-negative, as well as receptor-positive, breast cancer cells was treated with siRNA against CDK1 or CDK2 for 72 h and assessed for cell viability. The experiment was independently repeated three times. The error bars represent means ± SEM. P-values were calculated by two-tailed Student’s t test. Western blots showing CDK1, CDK2, and actin protein expression are shown.