Oncogenic alterations in multiple core signaling pathways are required for glioblastoma pathogenesis in vitro and in vivo
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ABSTRACT: Here, we use a series of genetically-defined murine cortical astrocytes with conditional inactivation of Rb/Pten and activated Kras to systematically investigate the individual and combinatorial roles of these pathways during gliomagenesis. We show that genetic disruption of all three pathways, which frequently occurs in human GBM, leads to maximal in vitro growth, migration, and invasion and produces stem-like transcriptomal profiles similar to the proneural subtype of human GBM. Genetic alterations in all three pathways are also required for efficient tumorigenesis in an orthotopic syngeneic allograft model system in vivo. These findings show that cortical astrocytes can form GBM and identify a potential model for proneural GBM that can be used to test subtype-specific therapies. Transcriptional profiling of transformed murine cortical astrocytes shows correlation between mutated genes, invasive capability, neural lineage, and human astrocytoma/GBM signatures. 10 samples
ORGANISM(S): Mus musculus
PROVIDER: GSE40265 | GEO | 2013/06/30
SECONDARY ACCESSION(S): PRJNA173364
REPOSITORIES: GEO
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