Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Proteasome inhibition blocks estrogen-dependent gene transcription by decreasing histone H2B monoubiquitination in human breast cancer cells

ABSTRACT: The estrogen receptor-alpha (ERα) determines breast cancer cell phenotype and is a prognostic indicator. A better understanding of the mechanisms controlling ERα function may uncover improved strategies for the treatment of breast cancer. Proteasome inhibition was previously reported to regulate estrogen-induced transcription but the mechanisms by which it influences ERα function remain controversial. In this study we investigated the transcriptome-wide effects of the proteasome inhibitor Velcade on estrogen-regulated transcription in MCF7 human breast cancer cells and demonstrate a specific global decrease in estrogen-induced transcription.

ORGANISM(S): Homo sapiens

PROVIDER: GSE30931 | GEO | 2011/11/22

SECONDARY ACCESSION(S): PRJNA146281

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Proteasome inhibition blocks estrogen-dependent gene transcription by decreasing histone H2B monoubiquitination in human breast cancer cells

Project description:The estrogen receptor-alpha (ERα) determines breast cancer cell phenotype and is a prognostic indicator. A better understanding of the mechanisms controlling ERα function may uncover improved strategies for the treatment of breast cancer. Proteasome inhibition was previously reported to regulate estrogen-induced transcription but the mechanisms by which it influences ERα function remain controversial. In this study we investigated the transcriptome-wide effects of the proteasome inhibitor Velcade on estrogen-regulated transcription in MCF7 human breast cancer cells and demonstrate a specific global decrease in estrogen-induced transcription. This set contains 12 microarray samples. 3 controls, 3 estrogen stimulated, 3 Bortezomib stimulated, 3 Bortezomib + estrogen stimulated

2011-11-22 | E-GEOD-30931 | biostudies-arrayexpress

Estrogen-dependent gene expression in human breast cancer cells relies upon proteosome-dependent monoubiquitination of histone H2B

2011-11-22 | GSE31118 | GEO

Estrogen-dependent gene expression in human breast cancer cells relies upon proteosome-dependent monoubiquitination of histone H2B

Project description:The estrogen receptor-alpha (ERÎ±) determines breast cancer cell phenotype and is a prognostic indicator. A better understanding of the mechanisms controlling ERÎ± function may uncover improved strategies for the treatment of breast cancer. Proteasome inhibition was previously reported to regulate estrogen-induced transcription but the mechanisms by which it influences ERÎ± function remain controversial. In this study we investigated the transcriptome-wide effects of the proteasome inhibitor Velcade on estrogen-regulated transcription in MCF7 human breast cancer cells and demonstrate a specific global decrease in estrogen-induced transcription. This set contains 21 microarray samples. 3 controls, 3 estrogen stimulated, 3 Bortezomib + estrogen stimulated, 2* 3 siRNA controls, 3 siRNA PSMB3 knockdowns, 3 siRNA PSMB5 knockdowns

2011-11-22 | E-GEOD-31118 | biostudies-arrayexpress

Cohesin is required for expression of the estrogen receptor-alpha (ESR1) gene

Project description:In this study we show that depletion of the cohesin subunit SMC3 or the Mediator subunit MED12 significantly impairs the ERα-regulated transcriptome. Surprisingly, SMC3 depletion appears to elicit this effect indirectly by rapidly decreasing ESR1 transcription and ERα protein levels. Moreover, we provide evidence that both SMC3 and MED12 colocalize on the ESR1 gene and are mutually required for occupancy as well as for transcriptional elongation. Finally, we show that extended proteasome inhibition decreases the mRNA expression of cohesin subunits which accompanies a decrease in ESR1 mRNA and ERα protein levels as well as estrogen-regulated transcription. Conclusions: These results identify the ESR1 gene as a cohesin/Mediator-dependent gene and indicate that this regulation may potentially be exploited for the treatment of estrogen-dependent breast cancer. This set contains 18 microarray samples with triplicates for each condition. 3 control siRNA, 3 control estrogen stimulated, 3 siRNA Med12 knockdown, 3 siRNA Med12 knockdown estrogen stimulated, 3 siRNA Smc3 knockdown, 3 siRNA Smc3 knockdown estrogen stimulated.

2013-05-20 | E-GEOD-38252 | biostudies-arrayexpress

Nuclear Estrogen Receptor alpha (ERα) interactome following estrogen and antiestrogen treatment.

Project description:The Estrogen Receptor alpha (ERα) controls key cellular functions in hormone responsive breast cancer by assembling in large functional multiprotein complexes. ERα ligands are classified as agonists and antagonist, according to the response they elicit, thus the molecular characterization of the of ERα nuclear iteractome composition following estrogen and antiestrogen stimulation whose is needed to understand their effects on estrogen target tissues, in particular breast cancer. To this aim interaction proteomics coupled to mass spectrometry (MS) was applied to map the ERα nuclear interacting partners in MCF7 breast cancer cell nuclei following estrogen and antiestrogen stimuli.

2020-09-02 | PXD018709 | Pride

MCF7 Cells: Control siRNA -E2 vs. Control siRNA +E2, Control siRNA -E2 vs. PES1 siRNA -E2,Control siRNA -E2 vs. PES1 siRNA +E2

Project description:The initiation of breast cancer is associated with increased expression of tumor-promoting estrogen receptor α (ERα) protein and decreased expression of tumor-suppressive ERβ protein. However, the mechanism underlying this process is unknown. Here we show that Pescadillo/PES1, an estrogen-inducible protein that is over-expressed in breast cancer, can regulate the balance between ERα and ERβ. PES1 enhances transcriptional activity of ERα and reduces that of ERβ, and modulates many estrogen-responsive genes. Consistent with this regulation of ERα and ERβ transcriptional activity, PES1 increases the stability of the ERα protein and decreases that of ERβ through the ubiquitin-proteasome pathway, mediated by the carboxyl terminus of Hsc70-interacting protein (CHIP). Moreover, PES1 can transform normal human mammary epithelial cells and is required for estrogen-induced breast tumor growth in nude mice. Further analysis of clinical samples showed that expression of PES1 correlates positively with ERα expression and negatively with ERβ expression, and predicts good clinical outcome in breast cancer. Our data demonstrate that PES1 contributes to breast tumor growth through regulating the balance between ERα and ERβ and may be a better target for the development of drugs that selectively regulate ERα and ERβ activities.

2012-06-10 | GSE38621 | GEO

Genome-wide activity of unliganded Estrogen Receptor alpha in breast cancer cells [RNA-Seq]

Project description:ERα is essential for the anti-proliferative response of breast cancer cells not only to estrogen antagonists, but also to estrogen withdrawal by means of aromatase inhibitors. We explored here one of the simplest explanation for this, consisting in the possibility that ERα may have a wide genomic function in absence of ligands. The genomic binding of ERα in the complete absence of estrogen was then studied using hormone-dependent MCF7 cells, by chromatin immunoprecipitation sequencing. From these data, 4.2K highly significant binding events were identified, which were further confirmed by comparing binding events in cells expressing ERα to cells silenced for ERα. Apo-ERα binding sites were distributed close to genes with functions associated to cell growth and epithelial maintenance and show significant overlap with binding of other transcription factors important for luminal epithelial breast cancer. Interestingly, we found that upon ERα silencing cognate gene transcription in absence of estrogen is downregulated and this is accompanied by increased H27Kme3 at ERα binding sites. RNA-Seq experiments showed that unliganded ERα controls basal transcription widely, including both coding and noncoding transcripts. Genes affected by ERα silencing can be easily functionally related to mammary epithelium differentiation and maintenance, especially when considering downregulated genes. Additional functions related to inflammatory and immune response was observed. Our data unravel unexpected actions of ERα in breast cancer cells and provide a novel framework to understand success and failure of hormone therapy in breast cancer. Examination of unligandend estrogen receptor alpha (aERα) DNA interactions in control and aERα siRNA treated MCF7 cells.

2014-03-03 | E-GEOD-53532 | biostudies-arrayexpress

Ctr9, a key subunit of PAFc, affects global estrogen signaling and drives ERalpha-positive breast tumorigenesis

Project description:The human RNA polymerase II-associated factor complex (hPAFc) and its individual subunits have been implicated in human diseases including cancer. However, its involvement in breast cancer cells awaits investigation. Using data mining and human breast cancer tissue microarrays, we found that Ctr9, the key scaffold subunit in hPAFc, is highly expressed in ERα+ luminal breast cancer and the high expression of Ctr9 correlates with poor prognosis. Knockdown of Ctr9 in ERα+ breast cancer cells almost completely erased estrogen regulated transcriptional response. At the molecular level, Ctr9 enhances ERα protein stability, promotes recruitment of ERα and RNAPII and stimulates transcription elongation and transcription-coupled histone modifications. Knockdown of Ctr9, but not other hPAFc subunits, alters the morphology, proliferative capacity and tamoxifen-sensitivity of ERα+ breast cancer cells. Together, our study reveals that Ctr9, a key subunit of hPAFc, is a central regulator of estrogen signaling that drives ERα+ breast tumorigenesis, rendering it a potential target for the treatment of ERα+ breast cancer.

2015-09-25 | GSE73388 | GEO

DOT1 Like Histone Lysine Methyltransferase (DOT1L) and Menin 1 (MEN1) interaction proteomics in breast cancer cell nuclei

Project description:Estrogen Receptor alpha (ERα) is a ligand-inducible transcription factor that mediates estrogen signaling in hormone-responsive breast cancer (BC) and is the primary target of specific anticancer therapies that although effective can generate resistance phenomena that represents a crucial problem in clinical management of patients affected by this disease. DOT1 Like Histone Lysine Methyltransferase (DOT1L) and Menin 1 (MEN1) have been identified as functional component of the ERα mechanism of action. To investigate the involvement of DOT1L and MEN1 in mediating ERα actions in hormone-responsive and endocrine-resistant BC, interaction proteomics was applied to map the DOT1l and MEN1 nuclear interacting partners in MCF7 breast cancer cell nuclei in order to the identifiy new possible therapeutic targets for a more effective pharmacological treatment of endocrine therapy-resistant tumors.

2022-08-12 | PXD026864 | Pride

Single-cell transcriptome analysis reveals estrogen signaling augments the mitochondrial folate pathway to coordinately fuel purine and polyamine synthesis in breast cancer cells (T47D)

Project description:Estrogen regulates diverse physiological effects and drives breast tumor progression by directly activating the estrogen receptor α (ERα). However, due to the stochastic nature of gene transcription and the resulting heterogeneous cellular responses, it is important to investigate estrogen-stimulated gene expression profiles at the single-cell level in order to fully understand how ERα regulates transcription in breast cancer cells. In this study, we performed single-cell transcriptome analysis on ERα-positive breast cancer cell lines following 17β-estradiol stimulation. We sequenced a total of 177 single-cell transcriptomes and observed robust gene expression diversity between individual cells.

2018-11-20 | GSE107863 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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