Fig. 2
From: Upregulation of FOXM1 leads to diminished drug sensitivity in myeloma
Constitutive overexpression of FOXM1 promotes growth and survival of myeloma cells in vitro. a Scheme of study design. FOXM1Hi and FOXM1N myeloma cells were generated using lentiviral gene transduction. Two HMCLs, designated CAG and XG1, were used. FOXM1 message levels in FOXM1Hi cells, relative to normal levels in FOXM1N cells, were significantly elevated in both CAG cells (~ 15 fold) and XG1 cells (~ 6-fold). FOXM1 protein levels were only moderately increased: ~ 50% and ~ 30% in CAG and XG1 cells, respectively. See Figure 4a in reference [12] for details. b Bar diagrams depicting percent FOXM1Hi and FOXM1N XG1 and CAG cells in S or G2/M phase of the active cell cycle. Cells were treated with thiostrepton (TS) or left untreated for use as control (Co). The result is consistent with the analysis of cell proliferation in Figure 4b of reference [12], showing that after 1 week in cell culture, the number of viable, actively proliferating FOXM1Hi cells was significantly higher than that of FOXM1N cells. c Cell cycle fractions determined by flow cytometry. Treatment of cells using thiostrepton (TS) resulted in a significant drop in cell proliferation, using two-way ANOVA for comparison. d Scatter plot demonstrating positive correlation of FOXM1 expression and myeloma proliferation in 244 Bz-treated patients from the Mayo Clinic. Tumor cell proliferation was scored with the assistance of a gene expression-based proliferation index (GPI) developed by Bergsagel et al. [20]. e Flow cytometric dye efflux histograms of CAG cells (left) and XG1 cells (right), demonstrating heightened ABC transporter drug pump activity in FOXM1Hi cells relative to FOXM1N cells. Percent differences in mean fluorescence intensity (MFI) were 16% in case of CAG and 18% in case of XG1