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E-GEOD-38392 - Targeting EWSR1-FLI1 oncogene induced protein kinase C beta abolishes Ewing sarcoma growth in vivo

Status
Released on 30 June 2012, last updated on 17 July 2012
Organism
Homo sapiens
Samples (7)
Array (1)
Protocols (8)
Description
Identification of druggable targets is a prerequisite for developing targeted therapies against Ewing sarcoma. We report the identification of Protein Kinase C Beta (PRKCB) as a protein specifically and highly expressed in Ewing sarcoma as compared to other pediatric cancers. Its transcriptional activation is directly regulated by the EWSR1-FLI1 oncogene. Getting insights in PRKCB activity we show that, together with PRKCA, it is responsible for the phosphorylation of histone H3T6, allowing global maintenance of H3K4 trimethylation on a variety of gene promoters. In the long term, PRKCB RNA interference induces apoptosis in vitro. More importantly, in xenograft mice models, complete impairment of tumor engraftment and even tumor regression were observed upon PRKCB inhibition, highlighting PRKCB as a most valuable therapeutic target. Deciphering PRKCB roles in Ewing sarcoma using expression profiling, we found a strong overlap with genes modulated by EWSR1-FLI1 and an involvement of RPKCB in regulating crucial signaling pathways. Altogether, we show that PRKCB may have two important independent functions and should be considered as highly valuable for understanding Ewing sarcoma biology and as a promising target for new therapeutic approaches in Ewing sarcoma. A673 Ewing cell line was treated for 72 hours by either control siRNA or siRNA directed against PRKCB or EWSR1-FLI1. Total RNAs were extracted and hybridized on HuGene1.1STv1 Affymetrix Arrays. Normalisation was performed using specific Brainarray Enrtez gene CDF file (v14.1).
Experiment type
transcription profiling by array 
Contacts
Franck Tirode <geo@ncbi.nlm.nih.gov>, Didier Surdez, Olivier Delattre
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-38392.idf.txt
Sample and data relationshipE-GEOD-38392.sdrf.txt
Raw data (1)E-GEOD-38392.raw.1.zip
Processed data (1)E-GEOD-38392.processed.1.zip
Array designA-GEOD-15640.adf.txt
R ExpressionSetE-GEOD-38392.eSet.r
Links