Inactivation of HMGcoA reductase by RNAi was sufficient to induce loss of a neoplastic phenotype. (A) HMGcoA reductase and pMYC protein expression in cells treated with siRNA. An MYC-induced lymphoma cell line was transfected with smart-pool siRNA (Dharmacon RNA Technologies) directed against HMGcoA reductase and compared with mock-transfected cells. Protein expression was analyzed 18 hours after treatment by Western analysis. (B) Cell survival upon siRNA knockdown of HMGcoA reductase. Cells were stained with trypan blue and analyzed for survival 30 hours after transfection with siRNA. (C-D) Single-cell FACS analysis of cells transfected with siRNA. Levels of expression of HMGcoA reductase, phosphorylated ERK1/2, and phosphorylated MYC after (C) control/mock transfection or (D) transfection with siRNA against HMGcoA reductase, as measured by FACS analysis. A 3-color clustering of cellular populations was performed in FlowJo, and unique populations were color coded. Cells that do not incorporate the siRNA are blue/purple. Cells that incorporate the siRNA are orange.