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Series GSE58421 Query DataSets for GSE58421
Status Public on Jun 01, 2016
Title Increased Protein Processing Gene Signature in HDACi-resistant cells predicts response to proteasome inhibitors.
Organism Homo sapiens
Experiment type Expression profiling by array
Summary 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.
Overall design 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.
Contributor(s) Mann KK, Miller WH Jr
Citation(s) 27185211
Submission date Jun 12, 2014
Last update date Jan 09, 2018
Contact name Koren Mann
Organization name Lady Davis Institute
Lab Dr. Koren Mann
Street address 3755 Cote Ste Catherine
City Montreal
State/province Quebec
ZIP/Postal code H3T1E2
Country Canada
Platforms (1)
GPL17077 Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version)
Samples (8)
GSM2208831 U937 ctl rep1
GSM2208832 U937 ctl rep2
GSM2208833 U937 2µM vor 12h rep1
BioProject PRJNA252564

Download family Format
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE58421_RAW.tar 24.0 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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