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Series GSE31258 Query DataSets for GSE31258
Status Public on Jan 19, 2014
Title Overcoming chemoresistance in B lymphoma cells: elucidating the role of NF-kB in caspase-independent apoptosis by transcriptomic assessment.
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Although therapy responsiveness to therapy in Burkitt lymphoma (BL) is high, relapsed disease and and chemoresistance remain a clinical challenge, and complete mechanisms underlying BL chemoresistance and how it can be circumvented is yet to be fully elucidated. In this study we present data showing that chymotrypsin-like serine proteases inhibitor Nα-tosyl-L-phenylalanine chloromethylketone (TPCK) and specific NF-κB inhibitor Bay-11 7082 can induce caspase-independent apoptosis in chemoresistant BL cells. We also demonstrate that both TPCK and Bay-11 7082-treatment leads to decreased NF-κB nuclear activity and that this is associated with sensitization of chemoresistant Burkitt lymphoma cells. Furthermore we investigated global transcriptional changes induced by Bay-11 7082 and TPCK in the DG-75 and Raji cell lines, respectively, by microarray analysis using Illumina BeadChips. TPCK-treatment of Raji and DG-75 cells resulted in 59 and 21 differently expressed genes, respectively, while Bay-11-treated Raji and DG-75 cells displayed 1403 and 8 differently expressed genes, respectively. Gene Ontology (GO) categorization confirmed enrichment of multiple GOs in Bay 11-treated Raji and DG-75 cells. Fifty percent of the 61 categories in Raji cells were categories sorting under Biological Processes and represented mostly increased gene expression. In DG-75 cells Bay-11 7082 induced significant gene ontology enrichment in only two categories, where the increased/decreased ratio was 1:1. Further unsupervised and supervised bioinformatics processing by Ingenuity Pathway Analysis indicated significant networks in response to TPCK and Bay 11 respectively, including association to NF-κB. Bay-11 7082 demonstrated deregulated NF-κB related members of receptor mediated cell death signaling, i.e TRAF2 and TRADD, as well as deregulated members of the NF-κB signaling pathway from the cytoplasmic compartment, i.e RELB, in Raji cells. Comparably NF-κB network analysis of Raji- and DG-75 cells treated with Bay-11 7082 and Raji cells treated with TPCK demonstrated deregulation of NF-κB target genes CD69 and IL8. These data indicates that NF-kB may play a role in overcoming chemoresistance in BL cells with defective classical apoptosis signaling.
 
Overall design NF-κB network analysis of Raji- and DG-75 cells treated with Bay-11 7082 and Raji cells treated with TPCK
 
Contributor(s) Ottosson-Wadlund A, Jitkaew S, Johansson I, Fucharoen S, Hedenfalk I, Fadeel B
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Submission date Aug 08, 2011
Last update date Aug 16, 2018
Contact name Ida Johansson
E-mail(s) ida.johansson@med.lu.se
Organization name Lund University
Department Oncology
Street address Department of Oncology Clinical Sciences Lund University BMC C13
City Lund
ZIP/Postal code SE-22184
Country Sweden
 
Platforms (1)
GPL6947 Illumina HumanHT-12 V3.0 expression beadchip
Samples (18)
GSM774710 Burkitt lymphoma cell line Raji 1 h rep1
GSM774711 Burkitt lymphoma cell line Raji 1 h rep2
GSM774712 Burkitt lymphoma cell line Raji 1 h rep3
Relations
BioProject PRJNA144827

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE31258_RAW.tar 6.2 Mb (http)(custom) TAR
GSE31258_non-normalized.txt.gz 3.1 Mb (ftp)(http) TXT
Processed data included within Sample table
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