Mountain View
biomedical and healthCAre Data Discovery Index Ecosystem
help Advanced Search
Title: Increased Protein Processing Gene Signature in HDACi-resistant cells predicts response to proteasome inhibitors      
dateReleased:
06-01-2016
description:
Epigenetic modifying enzymes are commonly mutated in diffuse large B cell lymphoma (DLBCL). Importantly, genetics abnormalities lead to inactivation of HAT, which tilt the balance in favor of decreased protein acetylation in DLBCL cells. This suggests that protein acetylation regulation is an important factor in DLBCL pathogenesis and a potential target for therapy. We developed resistant cell lines to the histone deacetylase inhibitor (HDACi) vorinostat, in order to better define molecular mechanisms of action of HDACi in lymphoma cells. We found that cells resistant to HDACi have increased protein synthesis and proteasomal degradation. Additionally, cells resistant to HDACi have acquired increased susceptibility to proteasome inhibitors and this correlates with activation of the unfolded protein response. Importantly, using transcriptional signatures found in our resistant lymphoma cell line model, we show that tumors from DLBCL patients treated but unresponsive to HDACi therapy undergo similar changes. Together, these data show, for the first time, that HDACi may be used to prime DLBCL for targeted therapy including proteasome inhibitors. Gene expression in U937 cells after 12h exposure to 2µM vorinostat and after development of resistance to 2 µM vorinostat, with and without vorinostat in the media.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-58421
refinement:
raw
alternateIdentifiers:
58421
keywords:
functional genomics
dateModified:
06-04-2016
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-GEOD-17077
name:
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version)
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-58421/E-GEOD-58421.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-58421/E-GEOD-58421.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE58421
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

Feedback?

If you are having problems using our tools, or if you would just like to send us some feedback, please post your questions on GitHub.