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Unliganded Estrogen Receptor beta (ERβ) interactome before and after RNAse treatment in human breast cancer cells nuclei.

ABSTRACT: The Estrogen Receptor beta (ERβ), is a member of the nuclear receptor superfamily of trancriptional regulators, with oncosuppressive activities, antagonizing hormone-induced carcinogenesis and inhibiting growth and oncogenic functions in breast cancers (BCs). It is able to exert specific biological functions also in the absence of estrogen stimuli. Interaction proteomics coupled to mass spectrometry (MS) was applied to deeply characterize the nuclear interactors cooperating with unliganded ERβ and the role of RNA in mediating these iteractions.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Tuula Nyman

LAB HEAD: Tuula Nyman

PROVIDER: PXD006720 | Pride | 2017-12-19

REPOSITORIES: Pride

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	Giovannicombinedsample1-3with10ppmaccuracy.xlsx	Xlsx
	Giovannicombinedsample4-6with10ppmaccuracy.xlsx	Xlsx
	Giovannicombinedsample7to9with10ppmaccuracy.xlsx	Xlsx
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Publications

Quantitative mapping of RNA-mediated nuclear estrogen receptor β interactome in human breast cancer cells.

Giurato Giorgio G Nassa Giovanni G Salvati Annamaria A Alexandrova Elena E Rizzo Francesca F Nyman Tuula A TA Weisz Alessandro A Tarallo Roberta R

Scientific data 20180306

The nuclear receptor estrogen receptor 2 (ESR2, ERβ) modulates cancer cell proliferation and tumor growth, exerting an oncosuppressive role in breast cancer (BC). Interaction proteomics by tandem affinity purification coupled to mass spectrometry was previously applied in BC cells to identify proteins acting in concert with ERβ to control key cellular functions, including gene transcription, RNA splicing and post-transcriptional mRNA regulation. These studies revealed an involvement of RNA in ER ...[more]

PMID: 29509190

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The nuclear receptor ERbeta engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading

Project description:Background: The RNA-binding protein Argonaute 2 (AGO2) is a key effector of RNAsilencing pathways, exerting a pivotal role in microRNA maturation and activity, that in the cell nucleus is able to modulate chromatin remodeling, transcriptional gene regulation and RNA splicing. The Estrogen Receptor beta (ERβ), a member of the nuclear receptor superfamily of trancriptional regulators, is endowed with oncosuppressive activities, antagonizing hormone-induced carcinogenesis and inhibiting growth and oncogenic functions in luminal-like breast cancers (BCs), where its expression correlates with a better prognosis of the disease. Results: Applying interaction proteomics coupled to mass spectrometry (MS) to characterize nuclear factors cooperating with ERβ in gene regulation, we identified AGO2 as a novel partner of ERβ in human BC cells. ERβ-AGO2 association was confirmed in vitro and in vivo both in the nucleus and cytoplasm. ChIP-Seq demonstrated AGO2 association to a large number of ERβ binding sites, and total and nascent RNA-Seq in ERβ+ vs ERβ- cells, and before and after AGO2 knock-down in ERβ+ cells, revealed a widespread involvement of this factor in ERβ-mediated regulation of gene transcription rate and RNA splicing. Moreover, isolation and sequencing by RIP-Seq of ERβ-associated long and small RNAs in the cytoplasm suggested involvement of the nuclear receptor in RISC loading, indicating that it may able to control directly also mRNA translation efficiency and stability. Conclusions: These results demonstrate that AGO2 is a pleiotropic functional partner of ERβ in BC cells, indicating that both factors are endowed with multiple roles in the control of BC cell functions.

2017-09-20 | PXD006280 | Pride

Estrogen Receptor beta (ERβ) interactome in triple negative breast cancer cells nuclei

Project description:Breast cancer (BC) is the second most common type of cancer in women and one of the leading causes of cancer-related deaths worldwide. BC classification is based on the detection of three main histological markers: estrogen receptor alpha (ERα), progesterone receptor (PR) and the amplification of epidermal growth factor receptor 2 (HER2/neu). A specific BC subtype, named triple-negative BC (TNBC), lacks the aforementioned markers but a fraction of them express the estrogen receptor beta (ERβ). To investigate the functional role of ERβ in these tumors, interaction proteomics coupled to mass spectrometry (MS) was applied to deeply characterize the nuclear interactors partners in MDA-MD-468 and HCC1806 TNBC cells.

2019-12-03 | PXD014468 | Pride

Identification of cytoplasmic proteins interacting with unliganded estrogen receptor α and β- in human breast cancer cells

Project description:Estrogen Receptor subtypes (ERα and ERβ) are transcription factors sharing similar structure, however, they often perform opposite roles in breast cancer’s cell proliferation and tumor progression. Besides the well-characterized genomic actions of ERs upon ligand binding, rapid non-genomic cytoplasmic changes together with the recently discovered ligand-free action of ERs are emerging as key regulators of tumorigenesis. The identification of cytoplasmic interaction partners of unliganded ERα and ERβ may help characterize the molecular basis of the extra-nuclear mechanism of action of these receptors, revealing novel mechanisms to explain their role in breast cancer response or resistance to endocrine therapy. To this aim, in this study, cytoplasmic extracts from stably expressing TAP-ERα and -ERβ MCF-7 cell clones were subjected to interaction proteomics in the absence of estrogen stimulation, leading to the identification of 84 and 142 proteins associated with unliganded ERα and ERβ, respectively. Functional analyses of ER subtype-specific interactomes revealed significant differences in the molecular pathways associated to each receptor in the cytoplasm. This work reports the first identification of the unliganded ERα and ERβ cytoplasmic interactomes in breast cancer cells, providing novel experimental evidence on the non-genomic effects of ERs in the absence of hormonal stimulus.

2015-03-11 | PXD001202 | Pride

Estrogen receptor β role in tumour suppression of triple negative breast cancer

Project description:Breast cancer (BC) is the most common cancer in women worldwide, and is classified in multiple subtypes, including the so called triple-negative BC (TNBC). This is characterized by lack of estrogen receptor alpha (ERα), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/neu), that represent common targets for BC treatment. Their absence limits the number of therapies that may be applied for TNBC treatment, suggesting the need to identify novel therapeutic targets against this disease. Several studies reported that the beta ER subtype (ERβ) is expressed in a sizeable fraction of TNBCs where its presence correlates with improved patient outcome. We evaluated ERβ expression in TNBC tissues by immunohistochemistry using two validated antibodies, demonstrating presence of this protein in 28% of samples. To investigate, in this context, the role of this estrogen receptor in TNBC biology, ERβ-expressing cell lines, representing different TNBC subtypes, were generated. Cellular and functional assays confirmed the antiproliferative activity of ERβ in TNBCs. Interaction proteomics revealed in BC nuclei the presence of several protein complexes associated with this receptor involved in chromatin remodeling, miRNA maturation and mRNA transcription. Transcriptome analyses pointed out tumor subtype-specific signaling pathways deregulation. Interestingly, among these the cholesterol biosynthesis pathway was commonly downregulated in all cell lines tested. Global analyses of ERβ binding to the genome showed its recruitment to regulatory sites of Sterol Regulatory Element-Binding Protein 1 (SREBP1), indicating a direct regulation of this pathway by the receptor. These findings suggest that drugs targeting components of cholesterol biosynthesis pathway may be new potential therapeutic options for TNBC treatment.

2019-12-03 | E-MTAB-8055 | biostudies-arrayexpress

Mapping ERβ genomic binding sites reveals unique genomic features and identifies EBF1 as an ERβ interactor [Gro-Seq]

Project description:The C4-12/Flag.ERβ cell line which stably expressed Flag.ERβ is used to study ERβ genomic functions without ERα interference. Mapping ERβ binding sites in these cells reveals ERβ unique distribution and motif enrichment patterns. Accompanying our mapping results, nascent RNA profiling is performed on cells at the same treatment time. The combined results allow the identification of ERβ target genes. Gene ontology analysis reveals that ERβ targets are enriched in differentiation, development and apoptosis. Concurrently, E2 treatment suppresses proliferation in these cells. Within ERβ binding sites, while the most prevalent binding motif is the canonical ERE, motifs of known ER interactors are also enriched in ERβ binding sites. Moreover, among enriched binding motifs are those of GFI, REST and EBF1, which are unique to ERβ binding sites in these cells. Further characterization confirms the association between EBF1 and the estrogen receptors, which favors the N-terminal region of the receptor. Furthermore, EBF1 negatively regulates ERs at the protein level. In summary, by studying ERβ genomic functions in our cell model, we confirm the anti-proliferative role of ERβ and discover the novel cross talk of ERβ with EBF1 which has various implications in normal physiology. C4-12/Flag.ERβ cells were treated with 10nM E2 (or ethanol as vehicle control) for 1 hour. Nuclei were extracted and processed with run-on assay. The resultant run-on RNA was reverse-transcribed to generate cDNA library which was subsequently sequenced by Illumina Genome Analyzer II or HiSeq2000. Two samples for each treatment were included in this experiment.

2013-06-21 | E-GEOD-48159 | biostudies-arrayexpress

Estrogen receptor β role in tumour suppression of triple negative breast cancer - ChIPseq experiment

2019-12-02 | E-MTAB-8056 | biostudies-arrayexpress

The nuclear receptor ERbeta engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading. Part 5

Project description:The RNA-binding protein Argonaute 2 (AGO2) is a key effector of RNA-silencing pathways It exerts a pivotal role in microRNA maturation and activity, and can modulate chromatin remodeling, transcriptional gene regulation and RNA splicing. The Estrogen Receptor beta (ERβ) is endowed with oncosuppressive activities, antagonizing hormone-induced carcinogenesis and inhibiting growth and oncogenic functions in luminal-like breast cancers (BCs), where its expression correlates with a better prognosis of the disease. Applying interaction proteomics coupled to mass spectrometry (MS) to characterize nuclear factors cooperating with ERβ in gene regulation, we identify AGO2 as a novel partner of ERβ in human BC cells. ERβ-AGO2 association was confirmed in vitro and in vivo both in the nucleus and in cytoplasm and is shown to be RNA-mediated. ChIP-Seq demonstrates AGO2 association to a large number of ERβ binding sites, and total and nascent RNA-Seq in ERβ+ vs ERβ- cells, and before and after AGO2 knock-down in ERβ+ cells, reveals a widespread involvement of this factor in ERβ-mediated regulation of gene transcription rate and RNA splicing. Moreover, isolation and sequencing by RIP-Seq of ERβ-associated long and small RNAs in the cytoplasm suggests involvement of the nuclear receptor in RISC loading, indicating that it may able to control directly also mRNA translation efficiency and stability.These results demonstrate that AGO2 can act as a pleiotropic functional partner of ERβ, indicating that both factors are endowed with multiple roles in the control of key cellular functions

2017-04-25 | E-MTAB-4359 | biostudies-arrayexpress

The nuclear receptor ERbeta engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading. Part 3

2016-12-31 | E-MTAB-4368 | biostudies-arrayexpress

The nuclear receptor ERbeta engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading. Part 4

2017-04-25 | E-MTAB-4363 | biostudies-arrayexpress

The nuclear receptor ERbeta engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading. Part 1

2016-10-31 | E-MTAB-4638 | biostudies-arrayexpress