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Series GSE22139 Query DataSets for GSE22139
Status Public on May 16, 2011
Title Bone morphogenetic protein-7 is a MYC target with pro-survival functions in childhood medulloblastoma
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Medulloblastoma (MB) is the most common malignant brain tumor in children, among whom overexpression or amplification of MYC oncogenes has been associated with poor clinical outcome. Although the MYC functions during normal development and oncogenesis in various systems have been extensively investigated, the transcriptional targets mediating MYC effects in MB are still elusive. Their identification and roles during MB onset and progression are important and will ultimately suggest novel potential therapeutic targets. cDNA microarray analysis was used to compare the effects of overexpressing and silencing MYC on the transcriptome of a MB-derived cell line. We identified 209 genes with potential relevance to MYC-dependent cellular responses in MB. Among the MYC-responsive genes, we found members of the bone morphogenetic protein (BMP) signaling pathway, which plays a crucial role during the development of the cerebellum. In particular, the cytokine gene BMP7 was identified as a direct target of MYC in MB cells. Similar to the effect induced by BMP7 silencing by siRNA, the use of a small-molecule inhibitor of the BMP/SMAD signaling pathway reduced cell viability in a panel of MB cells. Altogether, our findings indicate that high MYC levels drive BMP7 expression in MB to induce pro-survival and pro-proliferative cellular pathways. This observation suggests that targeting the BMP/SMAD pathway may be a new therapeutic concept for the treatment of childhood MB.
 
Overall design 6 samples (3 replicates for each sample): wild-type MB cell line, empty vector-transfected control cell line, 2 c-MYC-overexpressing clones, 1 clone upon c-MYC silencing, 1 silencing control cell line.
 
Contributor(s) Giulio F, Castelletti D, Arcaro A, Grotzer MA, Zoller S, Pruschy M, Schramm A, Schroeder C, Stearns D, Eggert A, Westermann F, Shalaby T
Citation(s) 21317922
Submission date Jun 04, 2010
Last update date Mar 25, 2019
Contact name Stefan Zoller
E-mail(s) szoller@env.ethz.ch
Organization name ETH Zurich
Department Genetic Diversity Centre
Street address Universitatstrasse 16
City Zurich
ZIP/Postal code 8092
Country Switzerland
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (18)
GSM550686 medulloblastoma, wt, rep1
GSM550687 medulloblastoma, wt, rep2
GSM550688 medulloblastoma, wt, rep3
Relations
BioProject PRJNA127579

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE22139_RAW.tar 85.5 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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