Figure 5  YAP induces expression of IGF2 and activation of Akt
(A) IGF2 was found to be up-regulated in the presence of YAP using microarray analysis, confirmed by quantitative RT-PCR. Irradiation induces IGF2 in GFP- and YAP-infected cells, but levels are significantly higher in YAP-infected CGNPs 3 hours post-irradiation.
(B) ELISA analysis of IGF2 production in GFP- or YAP-transduced control or irradiated CGNPs (3h). Statistically significant differences are indicated as (*) P < 0.05; (***) P < 0.001.
(C) Western blot analysis of IGF2 protein in GFP- or YAP-transduced control and irradiated CGNPs (3h).
(D) Box plot showing IGF2 mRNA expression obtained from exon array profiling of 103 primary human medulloblastomas, 9 fetal and 5 adult human control cerebella. IGF2 is highly expressed specifically in SHH-driven medulloblastomas (T test, p=3.553E-14). IGF1 is not specifically elevated in human SHH-associated medulloblastomas (Supplementary Figure 4).
(E) Western blot analysis of IGF2 protein in GFP-SmoA1 and YAP-SmoA1 mouse medulloblastomas.
(F) Immunohistochemical staining for IGF2 in medulloblastomas from non-irradiated (left) and irradiated (3h; right) GFP-SmoA1 and YAP-SmoA1 tumor bearing mice.
(G) Immunofluorescence analysis of Akt S473 phosphorylation and YAP protein in medulloblastomas from non-irradiated (left) and irradiated (3h; right) GFP-SmoA1 and YAP-SmoA1 tumor bearing mice.