Fig. 5

BMP7-induced transcriptional reconfiguration and sensitization of MGMT-expressing GSC to TMZ therapy. a Representative results of sqRT-PCR analysis of stemness and TMZ resistance-associated genes in GSC-500 μM TMZ modulated by the indicated treatments. The graph shows the mean values of percentage of mRNA expression levels of indicated genes in D431-500 μM TMZ treated with TMZ (35 μM), BMP7 (100 ng/ml) or their combination relative to those of untreated D431-500 μM TMZ. All values were normalized to those of the internal control gene β-actin, with values of treated D431-500 μM TMZ representing the % relative to that of untreated D431-500 μM TMZ, which was converted to 100 %. Data represent mean values ± SD of triplicate measurements in three independent experiments. *p < 0.05 and **p < 0.001 in relation to GSC-parental. b Analyses of gene expression profiles of BMP7-treated D431-parental and D431-500 μM TMZ. Probe set signals on expression array that were ≥ 1.25-fold different in BMP7-treated GSC cultures when compared to untreated GSC cultures were selected (P < 0.05). All plots show normalized gene expression values converted into a heatmap. The log2 of the fold difference is indicated by the heatmap scale at the bottom. Each column is an individual GSC samples (P = parental, T = 500 μM TMZ selected). Each row is a single probe set measurement of transcript abundance for an individual gene. The genes and gene functions are listed in the same order from top to bottom as the corresponding table (Table 2). c Kaplan-Meier survival curves of untreated, TMZ, BMP7, and combination-treated animals implanted with D431-parental intracranially. The treatment schedules and dosages were described in Methods. P-values were calculated using the Log-rank test. d Representative macrophotographic image of glioma xenografts treated with indicated therapy. e H-E staining of xenograft tumors from d