GEO DataSets

(Submitter supplied) Triple-negative breast cancer (TNBC) often develops resistance to single-agent treatment, which can be circumvented using targeted combinatorial approaches. Here, we demonstrate that the simultaneous inhibition of LOXL2 and BRD4 synergistically limits TNBC proliferation in vitro and in vivo. Mechanistically, LOXL2 interacts in the nucleus with the short isoform of BRD4 (BRD4S), MED1, and the cell cycle transcriptional regulator B-MyB. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

22 Samples

Download data: BED, BW, TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platforms:

GPL11154 GPL18573

65 Samples

Download data: WIG

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL11154 GPL18573

28 Samples

Download data: TXT

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL11154 GPL18573

35 Samples

Download data: WIG

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

2 Samples

Download data: WIG

(Submitter supplied) We performed RNA-seq of MDA-MB-231 cells that were treated with MS645 or JQ1 at 50 nM and 500 nM in an effort to understand how MS645 exerts such a profound cell growth inhibition on cancer cells.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

15 Samples

Download data: TDF, TXT

(Submitter supplied) Bromodomain-containing protein 4 (BRD4) is a cancer therapeutic target in many ongoing clinical trials disrupting primarily BRD4-regulated transcription programs. A critical role of BRD4 in cancer development has been reported and attributed mainly to the abundant long isoform (BRD4-L). Here we show, by isoform-specific knockdown and endogenous protein detection along with transgene expression, the less abundant BRD4 short isoform (BRD4-S) is oncogenic while BRD4-L is tumor-suppressive in breast cancer cell proliferation and migration as well as mammary tumor formation and metastasis. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL16791 GPL18573

48 Samples

Download data: BW, TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

4 Samples

Download data: H5

(Submitter supplied) BET bromodomain inhibitors (BBDI) are promising therapeutic agents in triple-negative breast cancer (TNBC). However, not all tumors respond and acquired resistance emerges rapidly even in the responders. Using CRISPR and small molecule inhibitor screens combined with comprehensive molecular profiling of BBDI response and resistance in TNBC cell lines, we identified numerous synthetic lethal interactions with BBDIs as well as genes that when deleted confer resistance. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

8 Samples

Download data: RDATA

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Other

Platform:

GPL11154

210 Samples

Download data: BED, BW, NARROWPEAK, TXT

(Submitter supplied) BET bromodomain inhibitors (BBDI) are promising therapeutic agents in triple-negative breast cancer (TNBC). However, not all tumors respond and acquired resistance emerges rapidly even in the responders. Using CRISPR and small molecule inhibitor screens combined with comprehensive molecular profiling of BBDI response and resistance in TNBC cell lines, we identified numerous synthetic lethal interactions with BBDIs as well as genes that when deleted confer resistance. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

62 Samples

Download data: TXT

(Submitter supplied) BET bromodomain inhibitors (BBDI) are promising therapeutic agents in triple-negative breast cancer (TNBC). However, not all tumors respond and acquired resistance emerges rapidly even in the responders. Using CRISPR and small molecule inhibitor screens combined with comprehensive molecular profiling of BBDI response and resistance in TNBC cell lines, we identified numerous synthetic lethal interactions with BBDIs as well as genes that when deleted confer resistance. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

61 Samples

Download data: BW, NARROWPEAK

(Submitter supplied) BET bromodomain inhibitors (BBDI) are promising therapeutic agents in triple-negative breast cancer (TNBC). However, not all tumors respond and acquired resistance emerges rapidly even in the responders. Using CRISPR and small molecule inhibitor screens combined with comprehensive molecular profiling of BBDI response and resistance in TNBC cell lines, we identified numerous synthetic lethal interactions with BBDIs as well as genes that when deleted confer resistance. more...

Organism:

Homo sapiens

Type:

Other

Platform:

GPL11154

44 Samples

Download data: TXT

(Submitter supplied) BET bromodomain inhibitors (BBDI) are promising therapeutic agents in triple-negative breast cancer (TNBC). However, not all tumors respond and acquired resistance emerges rapidly even in the responders. Using CRISPR and small molecule inhibitor screens combined with comprehensive molecular profiling of BBDI response and resistance in TNBC cell lines, we identified numerous synthetic lethal interactions with BBDIs as well as genes that when deleted confer resistance. more...

Organism:

Homo sapiens

Type:

Other

Platform:

GPL11154

19 Samples

Download data: TXT

(Submitter supplied) BET bromodomain inhibitors (BBDI) are promising therapeutic agents in triple-negative breast cancer (TNBC). However, not all tumors respond and acquired resistance emerges rapidly even in the responders. Using CRISPR and small molecule inhibitor screens combined with comprehensive molecular profiling of BBDI response and resistance in TNBC cell lines, we identified numerous synthetic lethal interactions with BBDIs as well as genes that when deleted confer resistance. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

16 Samples

Download data: BED, BW

(Submitter supplied) Oxidation of histone H3 at lysine 4 (H3K4ox) is catalyzed by lysyl oxidase–like 2 (LOXL2). This histone modification is enriched in heterochromatin in triple-negative breast cancer (TNBC) cells and has been linked to the maintenance of compacted chromatin. However, the molecular mechanism underlying this maintenance is still unknown. Here we show that LOXL2 interacts with RUVBL1, RUVBL2, BAF53, and DMAP1, a complex involved in the incorporation of the histone variant H2A.Z. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

15 Samples

Download data: BED, BEDGRAPH

(Submitter supplied) assess the efficacy of OTX015 (MK-8628) BET inhibitor in vitro and in vivo triple negative breast cancer models

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

18 Samples

Download data: TXT

(Submitter supplied) LCCC1122 is a window trial in stage I-IV TNBC patients scheduled to undergo definitive surgery (either lumpectomy, mastectomy or surgical resection of oligometastatic disease). Enrolled patients will receive 1.5 -2.0 mg of the MEK1/MEK2 inhibitor GSK1120212 (trametinib; Mekinist®) orally once daily for 7 days (with treatment initiation dependent on surgical schedule) prior to their surgery, with pre- and post- treatment tissue analyzed for kinome response and resistant signatures. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

28 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens; Mus musculus

Type:

Methylation profiling by genome tiling array; Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing; Genome variation profiling by high throughput sequencing

5 related Platforms

167 Samples

Download data: BED, CSV, IDAT, TXT, XLSX

(Submitter supplied) Targeting the dysregulated BRaf-MEK-ERK pathway in cancer has increasingly emerged in clinical trial design. Despite clinical responses in specific cancers using inhibitors targeting BRaf and MEK, resistance develops often involving non-genomic adaptive bypass mechanisms. Inhibition of MEK1/2 by trametinib in triple negative breast cancer (TNBC) patients induced dramatic transcriptional responses, including upregulation of receptor tyrosine kinases (RTKs) comparing tumor samples before and after one week of treatment. more...

Organism:

Homo sapiens

Type:

Genome variation profiling by high throughput sequencing

Platform:

GPL16791

2 Samples

Download data: XLSX