Figure 2

Mitotic kinases as therapeutic targets in medulloblastoma. (A) The Venn diagram shows the overlap of 29 kinases identified by gene expression analysis to have high expression in medulloblastoma with 95 kinases found to be important for medulloblastoma proliferation in the siRNA kinase screen. WEE1 was one of the 6 kinases in common between the two approaches. (B) Model of G2-M kinases that mediate Daoy cell proliferation. Kinases in red are the hits from the combination of gene expression analysis and the kinome-wide RNAi screen. (C) WEE1 mRNA expression in 90 medulloblastoma patient samples shows a significant increase when compared to normal adult cerebellum (Adult CB) by microarray analysis. There is no significant difference in WEE1 expression between the 4 subgroups of medulloblastoma (Wnt, Shh, Group 3 and Group 4). (D) Microarray analysis shows an increase in WEE1 mRNA expression in a cohort of pediatric medulloblastoma (Medullo), primitive neuroectodermal tumors (PNET), glioblastoma multiforme (GBM) and pediatric pilocytic astrocytoma (PA) when compared to normal brain specimens. (E) WEE1 protein levels are increased in six common medulloblastoma cell lines. UPN 514 and UPN 605 are from normal pediatric cerebellum lysates (Normal CB).