Combination knockdown of Mdm2 with etoposide treatment improves growth inhibition of breast cancer cells. Clonal MCF-7 cell line with mdm2 shRNA was treated with 2 μg/ml doxycycline (DOX) for three days to induce shRNA expression, followed by 10 nM estrogen (E2) for five days and 50 μM etoposide (ETOP) in the presence of DOX. (a) Number of cells was determined by Guava Viacount assay. 10,000 cells were seeded at beginning of treatments. (b) Fluorescence activated cell sorting (FACS). Cells were harvested, fixed in 30% ethanol, and cellular DNA was stained with propidium iodide. (c) A model illustrating that Mdm2 plays a central role in estrogen-mediated breast cancer cell proliferation.