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Transcriptional regulation by Fra-1 in triple negative breast cancers

ABSTRACT: Transcriptional regulation by Fra-1 in triple negative breast cancers

PROVIDER: PRJNA612051 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11292321.fastq.gz	Fastqsanger.gz
	SRR11292322.fastq.gz	Fastqsanger.gz
	SRR11292323.fastq.gz	Fastqsanger.gz
	SRR11292324.fastq.gz	Fastqsanger.gz
	SRR11292325.fastq.gz	Fastqsanger.gz

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Transcriptional regulation by Fra-1 in triple negative breast cancers

Project description:This SuperSeries is composed of the SubSeries listed below. All the data are described in the article "Fra-1 regulates its target genes via binding to remote enhancers without exerting major control on chromatin architecture in triple negative breast cancers" by Bejjani et al.

2021-02-23 | GSE146825 | GEO

Blocking Fra-1 sensitizes triple-negative breast cancer to olaparib

Project description:Fra-1 (FOSL1) is overexpressed in triple-negative breast cancer (TNBC). Fra-1 is a member of the activator protein 1 (AP-1) transcription factor complex, which plays crucial roles in tumor progression and treatment resistance. We have previously identified 118 proteins that interact with endogenous chromatin-bound Fra-1 in TNBC cells in a large screen, and these included PARP1(Poly (ADP-ribose) polymerase 1). PARP1 inhibitor olaparib is currently in clinical use for treatment of BRCA-mutated TNBC breast cancer. Here, we demonstrate that this interaction impacts the efficacy of olaparib treatment. We corroborate that PARP1 interacts with Fra-1, and we show that PARP1 downregulates Fra-1 and consequently reduces AP-1 transcriptional activity. Inhibition of PARP1, on the other hand, increases Fra-1 levels and enhances its transcriptional activity, which in turn can increase treatment resistance. However, by inhibiting Fra-1, we found that TNBC cells became sensitized to olaparib treatment. We compared Fra-1 chromatin binding sites with the Fra-1 and PARP1 regulated transcriptomes, and found that a large fraction of PARP1-regulated genes was dependent on Fra-1. We further show that PARP1 protein levels significantly correlate with Fra-1 in clinical breast cancer tumors, and we identify that high PARP1 expression is indicative of a poor clinical outcome in breast cancer patients overall, but not in basal-like tumors. In conclusion, by exploring the functionality of the Fra-1 and PARP1 interaction, we propose that targeting Fra-1 could serve as a therapeutic approach to improve olaparib treatment outcome for TNBC patients.

2022-04-21 | GSE149621 | GEO

Blocking Fra-1 sensitizes triple-negative breast cancer to olaparib

Project description:Blocking Fra-1 sensitizes triple-negative breast cancer to olaparib

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Consensus molecular classification of triple-negative breast cancers

Project description:Consensus molecular classification of triple-negative breast cancers

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Identification of Fra-1 and/or Fra-2 regulated genes in MDA-MB231 cells

Project description:In the paper "Fra-1 regulates its target genes via binding to remote enhancers without exerting major control on chromatin architecture in triple negative breast cancers" by Bejjani et al., we identified Fra-1 and/or Fra-2 target genes in MDA-MB-231 cells. si RNA against Fra-1 and against Fra-2 were transfected in MDA-MB-231 cells either independenlty or simultaneously to identify genes regulated specifically by Fra-1 or Fra-2 and genes regulated redundantly or complementarily by Fra-1 and Fra-2 total RNA were purified and biotinylated sense-strand cDNA were produced. cDNA targets were used to probe Affymetrix GeneChip Human Gene 2.0 ST arrays

2021-02-23 | GSE146823 | GEO

NG-Capture C analysis of 35 gene loci regulated by Fra-1 in MDA-MB-231 cells

Project description:In the article "Fra-1 regulates its target genes via binding to remote enhancers without exerting major control on chromatin architecture in triple negative breast cancers" by Bejjani et al., we used NG Capture-C approach to identify regulatory elements interacting with the promoters of 35 Fra-1 regulated genes in the triple negative breast cancer cell line MDA-MB-231

2021-02-23 | GSE146824 | GEO

BRCAness, SLFN11 and RB1 loss predict response to topoisomerase I inhibitors in triple negative breast cancers

Project description:Expression data from patient-derived xenografts of human triple-negative breast cancers

2019-12-28 | GSE142639 | GEO

Comparative Characterization of 3D Chromatin Organization in Triple-Negative Breast Cancers

Project description:Comparative Characterization of 3D Chromatin Organization in Triple-Negative Breast Cancers

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Consensus molecular classification of triple-negative breast cancers

Project description:The goal of this project was to establish a consensus molecular classification of triple-negative breast cancers (TNBC), ie. to identify TNBC robust subtypes. In order to optimize this process, we retrieved as much transcriptomic data as possible, measured by Affymetrix® microarrays (n = 886) and RNAseq (n = 699). In this last group, we included 48 new TNBC patients followed in our Cancer Centre. To our knowledge, this study is the largest one which aims at subtyping TNBC; it exploits a total of 1585 samples. Pooled data were standardized across different public datasets for both gene expression profiling technologies. Subsequently, clustering analysis revealed four robust subtypes.

2026-03-10 | GSE225002 | GEO

Transcriptomes of triple negative breast cancer enriched breast cancer cohort

Project description:Breast cancers enriched for the triple negative breast cancer phenotype with extensive clinico-pathological features were profiled to establish their comprehensive transcriptional profiles

2016-11-21 | E-MTAB-5270 | biostudies-arrayexpress

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