Figure 8: Notch/Heyl-induced PML degradation pathway promotes GIC characteristic.

(a) Neurosphere-forming abilities of GBM9 cells stably expressing indicated constructs. (b) Neurosphere-forming abilities of GBM9 cells stably expressing indicated constructs. (c) Neurosphere-forming abilities of GBM9 cells stably expressing indicated constructs. For panels (a–c), representative images of GIC neurospheres and their diameters (represented as mean±s.d. of three independent experiments, 30 neurospheres per group per experiment) are indicated on the bottom. Scale bars, 100 μm. (d) Effect of Notch-induced PML degradation pathway on the chemoresistant character of GICs. Apoptosis assay of GBM9 cells stably expressing indicated constructs and treated with TMZ and/or DAPT as described in Methods. (f) Apoptosis assay of GBM9 cells stably expressing indicated constructs and treated with TMZ. (f,g) Kaplan–Meier survival curves (upper panels) of mice implanted with 1 × 10³ GBM9 cells stably expressing indicated constructs, n=5 mice (f) and n=6 mice (g) for each indicated cell line (upper panels). The P values were determined by log-rank test. Representative light micrograph of brain tumours formed at indicated days after implantation are shown on the bottom panels. Brain tumours are marked by arrows. Scale bars, 2 mm. Data in panels a–e are mean±s.d. (**P<0.01 by t-test,***P<0.001) of three independent experiments.