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Series GSE63582 Query DataSets for GSE63582
Status Public on Jan 07, 2016
Title Response and resistance to BET bromodomain inhibitors in triple negative breast cancer [RNA-Seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Triple negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. Here we report the preferential and high sensitivity of TNBCs to BET bromodomain inhibitors such as JQ1 manifested by cell cycle arrest in early G1, apoptosis, and induction of markers of luminal epithelial differentiation in vitro and in vivo. The sensitivity of TNBC and other tumor types to BET inhibition establishes a rationale for clinical investigation, and a motivation to understand mechanisms of resistance. After engendering acquired resistance to BET inhibition in previously sensitive TNBCs, we utilized integrative approaches to identify a unique mechanism of epigenomic resistance to this epigenetic therapy. Resistant cells remain dependent on BRD4, confirmed by RNA interference. However, TNBC cells adapt to BET bromodomain inhibition by re-recruitment of unmutated BRD4 to super-enhancers, now in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify hyper-phosphorylation of BRD4 and strong association with MED1. Together, these studies provide a rationale for BET inhibition in TNBC and argue for combination strategies to anticipate clinical drug resistance.
Overall design RNA-Seq in parental and JQ1 resistant triple negative breast cancer (TNBC) in response to DMSO or JQ1 treatment over time
Contributor(s) Shu S, Lin CY, He HH, Bradner JE, Polyak K
Citation(s) 26735014
Submission date Nov 24, 2014
Last update date May 15, 2019
Contact name Kornelia Polyak
Phone 617-632-2106
Organization name Dana-Farber Cancer Institute
Department Medical Oncology
Lab Polyak
Street address 450 Brookline Ave
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (28)
GSM1553144 SUM159R_DMSO_24H_1
GSM1553145 SUM159R_DMSO_24H_2
GSM1553146 SUM159R_DMSO_3H_1
This SubSeries is part of SuperSeries:
GSE63584 Response and resistance to BET bromodomain inhibitors in triple negative breast cancer
BioProject PRJNA268320
SRA SRP050193

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Supplementary file Size Download File type/resource
GSE63582_TNBC_RNASEQ.FPKM.txt.gz 1.4 Mb (ftp)(http) TXT
GSE63582_TNBC_SUM149_RNASEQ.genes.fpkm_table.txt.gz 659.1 Kb (ftp)(http) TXT
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