Transcriptomics,Genomics

Dataset Information

25

A PDGFRα-driven mouse model of Glioblastoma reveals a Stathmin1-mediated mechanism of sensitivity to Vinblastine


ABSTRACT: Glioblastoma multiforme (GBM) is an aggressive primary brain cancer that includes focal amplification of PDGFRα and for which there are no effective therapies. Herein, we report the development of a genetically engineered mouse model of GBM based on autocrine, chronic stimulation of PDGFRα and the analysis of GBM signaling pathways using proteomics. We discovered the tubulin-binding protein Stathmin1 (STMN1) as a PDGFRα phospho-regulated target and that this mis-regulation conferred selective sensitivity to vinblastine (VB) cytotoxicity. Treatment of PDGFRα GBMs with VB in mice drastically prolonged survival and was dependent on STMN1. Our work provides a rationale for evaluating genotype-specific anti-microtubule drugs as cancer treatment in select GBM patient populations. Overall design: Total RNA was isolated from flash frozen tumors freshly excised from mice using Qiagen RNeasy RNA Isolation Kit. Gene expression analysis was conducted using the GeneChip® Mouse 2.0 ST Array (Affymetrix) at the Yale Center for Genome Analysis. Three biological replicates were profiles for each condition

INSTRUMENT(S): [MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version]

SUBMITTER: Hua-Jun Wu  

PROVIDER: GSE114438 | GEO | 2018-05-15

REPOSITORIES: GEO

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Publications


Glioblastoma multiforme (GBM) is an aggressive primary brain cancer that includes focal amplification of PDGFRα and for which there are no effective therapies. Herein, we report the development of a genetically engineered mouse model of GBM based on autocrine, chronic stimulation of overexpressed PDGFRα, and the analysis of GBM signaling pathways using proteomics. We discover the tubulin-binding protein Stathmin1 (STMN1) as a PDGFRα phospho-regulated target, and that this mis-regulation confers  ...[more]

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