Transcriptomics

Dataset Information

23

Transcription profiling of human KNS42 cells treated with the dual pI3-kinas/mTOR inhibitor PI-103


ABSTRACT: Sensitivity to temozolomide (TMZ) is restricted to a subset of glioblastoma patients, with the major determinant of resistance a lack of promoter methylation of the gene encoding the DNA methyltransferase MGMT, although other mechanisms are thought to be active. In a genome-wide screen of paediatric and adult glioma cells, we identified a co-ordinated upregulation of HOX gene expression in the MGMT-independent cell line KNS42. As a recent study has proposed a mechanism for this observation whereby transcriptional activation of the HOXA cluster is reversible by a PI3-kinase inhibitor through an epigenetic mechanism involving histone H3K27 trimethylation, we sought to investigate whether this was active in our system. We thus treated KNS42 cells for 24 hours with the dual PI3-kinase / mTOR inhibitor PI-103 at 5x IC50 and carried out gene expression profiling using Illumina HT-12 microarrays.

ORGANISM(S): Homo sapiens  

DISEASE(S): Glioblastoma

SUBMITTER: Anita Grigoriadis  

PROVIDER: E-TABM-890 | ArrayExpress | 2011-01-08

REPOSITORIES: ArrayExpress

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Publications

MGMT-independent temozolomide resistance in pediatric glioblastoma cells associated with a PI3-kinase-mediated HOX/stem cell gene signature.

Gaspar Nathalie N   Marshall Lynley L   Perryman Lara L   Bax Dorine A DA   Little Suzanne E SE   Viana-Pereira Marta M   Sharp Swee Y SY   Vassal Gilles G   Pearson Andrew D J AD   Reis Rui M RM   Hargrave Darren D   Workman Paul P   Jones Chris C  

Cancer research 20101008 22


Sensitivity to temozolomide is restricted to a subset of glioblastoma patients, with the major determinant of resistance being a lack of promoter methylation of the gene encoding the repair protein DNA methyltransferase MGMT, although other mechanisms are thought to be active. There are, however, limited preclinical data in model systems derived from pediatric glioma patients. We screened a series of cell lines for temozolomide efficacy in vitro, and investigated the differential mechanisms of r  ...[more]

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