A Systematic Substrate Screen Links Cyclin D-Dependent Kinases to Senescence Suppression in Cancer Cells through FOXM1

Gene expression (mRNA profiling) of U2OS osteosarcoma cells treated with 1 mM of the CDK4/6-specific inhibitor, PD0332991, versus vehicle (DMSO) for 4 hours Here, we monitored the early transcriptional response to acute inhibition of CDK4/6 catalytic activity. As PD0332991 substantially induced senescence in U2OS cells, we performed gene expression arrays from U2OS cells treated with or without PD0332991 for 4 hours. Although this did not result in significant changes in the cell cycle profile, it led to significant changes in global gene expression. 10 total samples were analyzed, i.e. we compared five PD0332991-treated versus five vehicle-treated U2OS cell samples (gene level).