RNA-Sequencing analysis of BET inhibitor resistant cell lines
Transcriptomics Dataset
FAIR Metrics
0 evaluations
General Information
| Accession | GSE87050 |
| Title | RNA-Sequencing analysis of BET inhibitor resistant cell lines |
| Description | Targeting BET bromodomain proteins utilizing small molecules in an emerging anti-cancer strategy with clinical evaluation of at least six inhibitors now underway. While MYC downregulation was initially proposed as a key mechanistic property of BET inhibitors, recent evidence suggests that additional anti-tumor activities are important. Using the E-Myc model of B-cell lymphoma we demonstrate that BET inhibition with JQ1 is a potent inducer of p53-independent apoptosis that occurs in the absence of effects on Myc gene expression. JQ1 skews the expression of pro-apoptotic (Bim) and anti-apoptotic (BCL-2/BCL-xL) BCL-2 family members to directly engage the mitochondrial apoptotic pathway. Consistent with this, Bim knockout or Bcl-2 overexpression inhibited apoptosis induction by JQ1. We identified lymphomas that were either intrinsically resistant to JQ1-mediated death or acquired resistance following in vivo exposure. Strikingly, in both instances BCL-2 was strongly upregulated and was concomitant with activation of RAS pathways. E-Myc lymphomas engineered to express activated Nras upregulated BCL-2 and acquired a JQ1-resistance phenotype. These studies provide important information on mechanisms apoptosis induction and resistance to BET-inhibition, while providing further rationale for the translation of BET inhibitors in aggressive B-cell lymphomas. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE87050 |
| Repository | Gene Expression Omnibus |
Related Datasets
GSE63582
Response and resistance to BET bromodomain inhibitors in triple negative breast cancer [RNA-Seq]
1
GSE63782
Transcriptional plasticity promotes primary and acquired resistance to BET bromodomain inhibition
1
GSE77988
BET Bromodomain inhibition promotes neurogenesis while inhibiting gliogenesis in neural progenitor cells
1
GSE82329
Adaptation of the Kinome Promotes Resistance to BET Bromodomain Inhibitors in Ovarian Cancer
1
GSE83660
High Resolution Mapping of RNA Polymerases Identifies Mechanisms of Sensitivity and Resistance to BET Inhibitors in t(8;21) AML
1
Tools
used to analyze the dataset
Canned Analyses
generated with the dataset
FAIR Evaluation
Sorry, you must be signed in to evaluate this object.
