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Series GSE68615 Query DataSets for GSE68615
Status Public on Jun 12, 2017
Title An autoregulatory RelB:p50 NF-κB pathway perpetuates pro-survival TNF response in multiple myeloma
Organism Mus musculus
Experiment type Expression profiling by array
Summary Pro-inflammatory cytokines were shown to promote growth and survival of cancerous cells. TNF induced RelA:p50 NF-κB dimer via the canonical pathway is thought to link inflammation with cancer. Integrating biochemical and computational studies we identify that deficiency of non-canonical signal transducer p100 triggers a positive autoregulatory loop, which instead perpetuates an alternate RelB:p50 containing NF-κB activity upon TNF treatment. TNF stimulated RelB:p50 dimer is sufficient for mediating NF-κB target gene-expressions and suppressing apoptotic cellular death independent of principal NF-κB subunit RelA. We further demonstrate that activating mutations in non-canonical NF-κB module deplete multiple myeloma cells of p100, thereby, provoking autoregulatory RelB:p50 activation. Finally, autoregulatory control reinforces protracted pro-survival NF-κB response, albeit comprising of RelB:p50, upon TNF priming that protects myeloma cells with dysfunctional p100 from subsequent apoptotic insults. In sum, we present evidence for positive autoregulation mediated through the NF-κB system and its potential involvement in human neoplasm.
Overall design Total RNA isolated from biological replicate samples comprising of untreated and 6h TNF (10ng/ml) treated WT, Rela-/-Nfkb2-/- and Rela-/-Relb-/-Rel-/- MEFs were analyzed for global gene expression levels
Contributor(s) Basak S, Roy P, Chatterjee B, Sarkar UA
Citation(s) 27641334
Submission date May 06, 2015
Last update date Jun 14, 2018
Contact name Soumen Basak
Organization name National Institute of Immunology
Department Infection and immunity
Lab Systems Immunology Laboratory
Street address Aruna Asaf Ali Marg
City New Delhi
State/province Delhi
ZIP/Postal code 110067
Country India
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (12)
GSM1677124 WT untreated replicate 1
GSM1677125 WT untreated replicate 2
GSM1677126 WT 6h TNF replicate 1
BioProject PRJNA283207

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
GSE68615_RAW.tar 3.1 Mb (http)(custom) TAR
GSE68615_non-normalized_part1.txt.gz 2.0 Mb (ftp)(http) TXT
Processed data included within Sample table

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