Figure 8.
Effects of combined MYCN/ALK signaling on the expression of marker genes for apoptosis, neuron differentiation, early sympathetic neuroblasts, proliferation, and mitosis analyzed by qRT-PCR; effects of SKP2 inhibition on the proliferation of MYCN/ALKF1174L neuroblasts. A, Differential gene expression between MYCN/ALKF1174L-transfected and ALKF1174L-transfected 8d cultures analyzed by qRT-PCR (mean ± SE; *p < 0.05; **p < 0.01; statistical analysis by relative expression software tool). B, E7 sympathetic ganglion cells were transfected with expression vectors for GFP, ALKF1174L, and MYCN. Cultures were supplemented at 5 dic with 10 μm SKP2 inhibitor SKPin C1 in DMSO or with DMSO alone and analyzed by GFP/Th/EdU triple immunostaining after 8 dic for the percentage of EdU-labeled proliferating MYCN/ALKF1174L neuroblasts. SKP2 inhibition resulted in a virtually complete proliferation block (mean ± SEM; n = 3; ***p < 0.001).