Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Interplay between AP-1 and ERalpha in regulating gene expression and proliferation networks in breast cancer cells

ABSTRACT: Estrogen receptor alpha (ERalpha) is a ligand-dependent transcription factor that plays an important role in breast cancer. Estrogen-dependent gene regulation by ERalpha can be mediated by interaction with other DNA-binding proteins, such as activator protein-1 (AP-1). The nature of such interactions in mediating the estrogen response in breast cancer cells remains unclear. Here we show that knockdown of c-Fos, a component of the transcription factor AP-1, attenuates the expression of 37% of all estrogen-regulated genes, suggesting that AP-1 is a fundamental factor for ERalpha-mediated transcription. Additionally, knockdown of c-Fos affected the expression of a number of genes that were not regulated by estrogen. Pathway analysis reveals that silencing of c-Fos downregulates an E2F1-dependent pro-proliferative gene network. Thus, modulation of the E2F1 pathway by c-Fos represents a novel mechanism by which c-Fos enhances breast cancer cell proliferation. Furthermore, we show that c-Fos and ERalpha can cooperate in regulating E2F1 gene expression by binding to regulatory elements in the E2F1 promoter. To start to dissect the molecular details of the cross-talk between AP-1 and estrogen signaling, we identify a novel ERalpha/AP-1 target, PKIB (cAMP-dependent protein kinase inhibitor-beta), which is overexpressed in ERalpha-positive breast cancer tissues. Knockdown of PKIB by siRNA results in drastic growth suppression of breast cancer cells. Collectively, our findings support AP-1 as a critical factor that governs estrogen-dependent gene expression and breast cancer proliferation programs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE36586 | GEO | 2012/08/06

SECONDARY ACCESSION(S): PRJNA153755

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Interplay between AP-1 and ERalpha in regulating gene expression and proliferation networks in breast cancer cells

Project description:Estrogen receptor alpha (ERalpha) is a ligand-dependent transcription factor that plays an important role in breast cancer. Estrogen-dependent gene regulation by ERalpha can be mediated by interaction with other DNA-binding proteins, such as activator protein-1 (AP-1). The nature of such interactions in mediating the estrogen response in breast cancer cells remains unclear. Here we show that knockdown of c-Fos, a component of the transcription factor AP-1, attenuates the expression of 37% of all estrogen-regulated genes, suggesting that AP-1 is a fundamental factor for ERalpha-mediated transcription. Additionally, knockdown of c-Fos affected the expression of a number of genes that were not regulated by estrogen. Pathway analysis reveals that silencing of c-Fos downregulates an E2F1-dependent pro-proliferative gene network. Thus, modulation of the E2F1 pathway by c-Fos represents a novel mechanism by which c-Fos enhances breast cancer cell proliferation. Furthermore, we show that c-Fos and ERalpha can cooperate in regulating E2F1 gene expression by binding to regulatory elements in the E2F1 promoter. To start to dissect the molecular details of the cross-talk between AP-1 and estrogen signaling, we identify a novel ERalpha/AP-1 target, PKIB (cAMP-dependent protein kinase inhibitor-beta), which is overexpressed in ERalpha-positive breast cancer tissues. Knockdown of PKIB by siRNA results in drastic growth suppression of breast cancer cells. Collectively, our findings support AP-1 as a critical factor that governs estrogen-dependent gene expression and breast cancer proliferation programs. MCF-7 cells were transfected with a control siRNA or with the pool of siRNAs targeting c-Fos for 72 h and were then treated with vehicle or E2 for 24 h, and global gene expression profiles were assessed. Three or four biological replicates were used for each group.

2012-08-05 | E-GEOD-36586 | biostudies-arrayexpress

An H3K4me3 reader, BAP18 as an adaptor of COMPASS-like core subunits co-activates ERa action to confer to tamoxifen resistance in breast cancer

Project description:Estrogen receptor alpha (ERalpha signaling pathway is essential for ERalpha positive breast cancer progression and endocrine therapy resistance. BPTF associated protein of 18kDa (BAP18) has been recognized as a crucial H3K4me3 reader. However, the whole genomic occupation of BAP18 and its biological function in breast cancer are still elusive. Here, we found that higher expression of BAP18 in ERalpha positive breast cancer is positively correlated with poor prognosis. ChIP-seq analysis further demonstrated that the half estrogen response elements (EREs) and the CCCTC binding factor (CTCF) binding sites are the significant enrichment sites found in estrogen-induced BAP18 binding sites. In addition, we provide the evidence to demonstrate that BAP18 as a novel co-activator of ERalpha is required for the recruitment of COMPASS-like core subunits to cis-regulatory element of ERalpha target genes in breast cancer cells. BAP18 is recruited to the promoter regions of estrogen-induced genes, accompanied with the enrichment of the lysine 4-trimethylated histone H3 tail (H3K4me3) in the presence of E2. Furthermore, BAP18 promotes cell growth and confers to ERalpha antagonist tamoxifen resistancein ERalpha positive breast cancer. Our data suggest that BAP18 facilitates the association between ERalpha and COMPASS-like core subunits, which might be an essential epigenetic therapeutic target for breast cancer.

2020-11-09 | GSE144641 | GEO

Estrogen effects on MCF-7 breast cancer cells co-expressing ERa and ERb

Project description:Two subtypes of the estrogen receptor, ERalpha and ERbeta, mediate the actions of estrogens, and the majority of human breast tumors contain both ERalpha and ERbeta. To examine the possible interactions and modulatory effects of ERbeta on ERalpha activity, we have used adenoviral gene delivery to produce human breast cancer (MCF-7) cells expressing ERbeta, along with their endogenous ERalpha. We have examined the effects of ERβ expression on genome-wide gene expression by Affymetrix GeneChip microarrays. We find that ERbeta modulated estrogen gene expression on nearly 24% of E2-stimulated genes but only 8% of E2-inhibited genes. We find that ERbeta modulation is gene-specific, enhancing or counteracting ERalpha regulation for distinct subsets of estrogen target genes. Introduction of ERbeta into ERalpha-containing cells induced up/down-regulation of many estrogen target in the absence of any added ligand. In addition, ERbeta presence elicited the expression of a unique set of genes that were not regulated by ERalpha alone. ERbeta modulated the expression of genes in many functional categories, but the greatest numbers were associated with transcription factor and signal transduction pathways. Regulation of multiple components in the TGF beta, SDF1, and semaphorin pathways, may contribute to the suppression of proliferation observed with ERbeta both in the presence and absence of estrogen. Hence, ERbeta modulates ERalpha gene regulation in diverse ways that may contribute to its growth-inhibiting beneficial effects in breast cancer Keywords: modulatory effects of ERb on ERa

2006-08-10 | GSE4006 | GEO

LncRNA AGPG confers endocrine resistance in breast cancer by promoting E2F1 activity

Project description:Resistance to endocrine therapy represents a major threat to patients with estrogen receptor α positive (ERα+) breast cancer. The development of resistance is mainly through activating E2F signaling. However, the mechanisms that govern E2F1 activity in these resistant cells remain poorly understood. Here, we identify Actin Gamma 1 Pseudogene 25 (AGPG) as a lncRNA whose expression is driven by epigenomic activation of enhancer in endocrine resistant breast cancer cells. High expression of AGPG is associated with poor survival of ERα+ breast cancer, especially in patients receiving endocrine therapy. Stable knockdown and overexpression of AGPG demonstrate that AGPG promotes endocrine resistance, cell cycle progression, cell proliferation in vitro and in vivo. AGPG functions by direct binding purine rich element binding protein α (PURα), a transcription factor repressing E2F1 signaling and sensitized ERα+ breast cancer cells to endocrine therapy. Via binding to the region responsible for PURα/E2F1 interaction in PURα protein, AGPG releases E2F1 from PURα, leading to activation of E2F1 signaling in ERα+ breast cancer cells. Clinically, E2F1 target genes are strongly correlated with AGPG and PURα expression. Thus, our study reveals AGPG as a promising biomarker and potential therapeutic target in breast cancer.

2023-07-12 | GSE218130 | GEO

Combinatorial regulation of estrogen receptor alpha-responsive promoters

Project description:In breast cancer and normal estrogen target tissues, estrogen receptor alpha (ERalpha) signaling results in establishment of spatiotemporal patterns of gene expression. A time-course series of ChIP-chip experiments were performed to identify direct ERalpha target genes and determine whether these targets were transcriptionally activated or repressed by ERalpha. Keywords: Time-course ChIP-chip

2006-02-03 | GSE3987 | GEO

Transcription profiling of human cancer cell line MCF-7 - estrogen effects where MCF7 is co-expressing ERa and ERb

Project description:Two subtypes of the estrogen receptor, ERalpha and ERbeta, mediate the actions of estrogens, and the majority of human breast tumors contain both ERalpha and ERbeta. To examine the possible interactions and modulatory effects of ERbeta on ERalpha activity, we have used adenoviral gene delivery to produce human breast cancer (MCF-7) cells expressing ERbeta, along with their endogenous ERalpha. We have examined the effects of ERÎ² expression on genome-wide gene expression by Affymetrix GeneChip microarrays. We find that ERbeta modulated estrogen gene expression on nearly 24% of E2-stimulated genes but only 8% of E2-inhibited genes. We find that ERbeta modulation is gene-specific, enhancing or counteracting ERalpha regulation for distinct subsets of estrogen target genes. Introduction of ERbeta into ERalpha-containing cells induced up/down-regulation of many estrogen target in the absence of any added ligand. In addition, ERbeta presence elicited the expression of a unique set of genes that were not regulated by ERalpha alone. ERbeta modulated the expression of genes in many functional categories, but the greatest numbers were associated with transcription factor and signal transduction pathways. Regulation of multiple components in the TGF beta, SDF1, and semaphorin pathways, may contribute to the suppression of proliferation observed with ERbeta both in the presence and absence of estrogen. Hence, ERbeta modulates ERalpha gene regulation in diverse ways that may contribute to its growth-inhibiting beneficial effects in breast cancer Experiment Overall Design: MCF-7 cells expressing endogenous ERalpha were infected with adenovirus carrying either estrogen receptor beta (AdERb) or no insert (Ad) at multiplicity of infection (moi) of 5 or 50. Cells were infected with adenovirus for a period of 48hr before treatment with ligand (vehicle control or 10nM 17beta-estradiol) for a additional period of 24hr before harvest.

2009-04-24 | E-GEOD-4006 | biostudies-arrayexpress

Mufudza2012 - Estrogen effect on the dynamics of breast cancer

Project description:Mufudza2012 - Estrogen effect on the dynamics of breast cancer This deterministic model shows the dynamics of breast cancer with immune response. The effects of estrogen are incorporated to study its effects as a risk factor for the disease. This model is described in the article: Assessing the effects of estrogen on the dynamics of breast cancer. Mufudza C, Sorofa W, Chiyaka ET. Comput Math Methods Med 2012; 2012: 473572 Abstract: Worldwide, breast cancer has become the second most common cancer in women. The disease has currently been named the most deadly cancer in women but little is known on what causes the disease. We present the effects of estrogen as a risk factor on the dynamics of breast cancer. We develop a deterministic mathematical model showing general dynamics of breast cancer with immune response. This is a four-population model that includes tumor cells, host cells, immune cells, and estrogen. The effects of estrogen are then incorporated in the model. The results show that the presence of extra estrogen increases the risk of developing breast cancer. This model is hosted on BioModels Database and identified by: BIOMD0000000642. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

2017-07-26 | BIOMD0000000642 | BioModels

Cellular reprogramming by the conjoint action of ERalpha, FOXA1, and GATA3 to a ligand inducible growth state

Project description:Despite the role of the estrogen receptor alpha (ERalpha) pathway as a key growth driver for breast cells, the phenotypic consequence of exogenous introduction of ERalpha into ERalpha-negative cells paradoxically has been growth inhibition. We map the binding profiles of ERalpha and its interacting transcription factors (TFs), FOXA1 and GATA3 in MCF-7 breast carcinoma cells. We observe that these three TFs form a functional enhanceosome and cooperatively modulate the transcriptional networks previously ascribed to ERalpha alone. We demonstrate that these enhanceosome occupied sites are associated with optimal enhancer characteristics with highest p300 coactivator recruitment, RNA Pol II occupancy, and chromatin opening. The enhancesome binding sites appear to regulate the genes driving core ERalpha function. Most importantly, we show that the transfection of all three TFs was necessary to reprogramme the ERalpha-negative MDA-MB-231 and BT-459 cells to restore the estrogen responsive growth and to transcriptionally resemble the estrogen treated ERalpha-positive MCF-7 cells. Cumulatively, these results suggest that all the enhanceosome components comprising ERalpha, FOXA1 and GATA3 are necessary for the full repertoire of cancer associated effects of the ERalpha. Illumina HumanRef-8 v3 Expression BeadChip was used to measure the gene expression levels from ERalpha negative breast cancer cell MDA-MB-231 with different transfections: with vector control, with ERalpha only, or with ERalpha+FOXA1+GATA3 combined.

2011-09-04 | E-GEOD-30574 | biostudies-arrayexpress

ERα gene expression profile in MCF7 cells

Project description:This submission is a part of two separate studies: a study of estrogen receptor-alpha (ERalpha)-mediated gene expression in response to different ligands and a study examining the roles of ERalpha and ERbeta in gene regulation in breast cancer cells.

2013-12-01 | GSE45557 | GEO

Cellular reprogramming by the conjoint action of ERalpha, FOXA1, and GATA3 to a ligand inducible growth state

2011-09-05 | GSE30574 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data