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Heat Shock Factor 1 (HSF1) acquires transcriptional competence under 17b-estradiol in ERa-positive breast cancer cells [RNA-seq]

ABSTRACT: Heat Shock Transcription Factor 1 (HSF1) is a well-known regulator of gene expression during acute environmental stress that enables the cells to survive. Its high level in estrogen receptor-positive breast cancer patients correlated with a worse prognosis. Here, we demonstrated that 17β-estradiol (E2) as well as bisphenol A (BPA) and propyl pyrazole triol (PPT, ERα agonist) led to HSF1 phosphorylation on S326 in ERα positive mammary breast cancer cells, but not in ERα-negative ones. We showed that ERK1/2 signaling was involved in this process and down-regulation of ERα expression abrogated it. E2activated HSF1 was transcriptionally potent. Chip-Seq and RNA-Seq analyses revealed that it could modulate the expression of several genes known to be essential for breast cancer cells growth and/or ERα action, i.e. HSPB8, LHX4, PRKCE, WWC1, and GREB1. Our findings indicate that a positive feedback loop between ERα and HSF1 signaling may exist which support the growth of estrogen-dependent tumors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE137559 | GEO | 2019/10/05

REPOSITORIES: GEO

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Heat Shock Factor 1 (HSF1) acquires transcriptional competence under 17b-estradiol in ERa-positive breast cancer cells [ChIP-seq]

Project description:Heat Shock Transcription Factor 1 (HSF1) is a well-known regulator of gene expression during acute environmental stress that enables the cells to survive. Its high level in estrogen receptor-positive breast cancer patients correlated with a worse prognosis. Here, we demonstrated that 17β-estradiol (E2) as well as bisphenol A (BPA) and propyl pyrazole triol (PPT, ERα agonist) led to HSF1 phosphorylation on S326 in ERα positive mammary breast cancer cells, but not in ERα-negative ones. We showed that ERK1/2 signaling was involved in this process and down-regulation of ERα expression abrogated it. E2activated HSF1 was transcriptionally potent. Chip-Seq and RNA-Seq analyses revealed that it could modulate the expression of several genes known to be essential for breast cancer cells growth and/or ERα action, i.e. HSPB8, LHX4, PRKCE, WWC1, and GREB1. Our findings indicate that a positive feedback loop between ERα and HSF1 signaling may exist which support the growth of estrogen-dependent tumors.

2019-10-05 | GSE137558 | GEO

Estrogen receptor α-mediated signaling inhibits type I interferon response to promote breast cancer

Project description:To investigate the molecular mechanisms by which estrogen receptor α (ERα) inhibits type I IFN-induced signaling. We identified genes induced by ERα signaling using data obtained from RNA-seq of MCF7 cells treated or untreated with selective ERα agonist propyl pyrazole triol (PPT).

2022-05-18 | GSE203058 | GEO

Uterine Transcriptional Profile Following Treatment with Estradiol or Synthetic Estrogens Diethylstilbestrol and Propyl Pyrazole Triol

Project description:Transcriptional responses in ovariectomized mouse uterine tissue to estradiol (E2) and diethylstilbestrol (DES), known long-acting estrogens, and propyl pyrazole triol (PPT), an ER-alpha selective estrogen, were profiled. Profiles were used together with those from other estrogens to derive a biomarker panel.

2015-10-01 | GSE61921 | GEO

A super enhancer-controlled BRD4/ERα-RET-ERα positive feedback loop promotes ERα-positive breast cancer [ChIP-seq]

Project description:Dysregulated estrogen and estrogen receptor (ER)-induced gene transcription is tightly associated with estrogen receptor alpha (ERα)-positive breast carcinogenesis. ERα-occupied enhancers, particularly super enhancers, have been suggested to play a vital role in such transcriptional events. However, the landscape of ERα-occupied super enhancers (ERSEs) as well as key super enhancer-associated genes remain to be fully characterized. Here, we defined the landscape of ERSEs in MCF7, a ERα-positive breast cancer cell line, and demonstrated that bromodomain protein BRD4 is a master regulator of the transcriptional activation of ERSE and cognate ERα-target genes. Furthermore, RET, a member of the tyrosine protein kinase family of proteins, was identified to be a key target gene of BRD4-regulated ERSEs, which is vital for estrogen/ ERα-induced gene transcriptional activation and malignant phenotypes through activating the Ras-Raf-MEK-ERK-p90RSK-ERα phosphorylation cascade. Accordingly, combination therapy with BRD4 and RET inhibitors exhibited synergistic effects on suppressing ERα-positive breast cancer both in vitro and in vivo. Taken together, our data uncovered the critical role of a super enhancer-associated BRD4/ERα-RET-ERα positive feedback loop in ERα-positive breast cancer, and targeting components in this loop will provide new therapeutic avenue for treating ERα-positive breast cancer in the clinic.

2022-10-19 | GSE186645 | GEO

A super enhancer-controlled BRD4/ERα-RET-ERα positive feedback loop promotes ERα-positive breast cancer [RNA-seq]

2022-10-19 | GSE186644 | GEO

A super enhancer-controlled BRD4/ERα-RET-ERα positive feedback loop promotes ERα-positive breast cancer [GRO-seq]

2022-10-19 | GSE186643 | GEO

Growth Factor Stimulation Induces a Distinct ERα Cistrome Underlying Breast Cancer Endocrine Resistance

Project description:Estrogen receptor alpha (ERα) expression in breast cancer is predictive of response to endocrine therapy, however resistance is common in ERα-positive tumors that over-express the growth factor receptor ERBB2. Even in the absence of estrogen, ERα can be activated by growth factors including the epidermal growth factor (EGF). EGF induces a transcriptional program distinct from estrogen, however the mechanism of the stimulus-specific response is unknown. Here we show that the EGF-induced ERα genomic targets, its cistrome, are distinct from those induced by estrogen in a process dependent on the transcription factor AP-1. The EGF-induced ERα cistrome specifically regulates genes found over-expressed in ERBB2-positive human breast cancers. This provides a potential molecular explanation for the endocrine therapy resistance seen in ERα-positive breast cancers that over-express ERBB2. These results suggest a central role for ERα in hormone-refractory breast tumors dependent on growth factor pathway activation and favors the development of therapeutic strategies completely antagonizing ERα as opposed to blocking its estrogen responsiveness alone.

2010-12-29 | GSE26081 | GEO

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

The effect of miRNA overexpression on gene expression profile of MCF-7 cells

Project description:To identify microRNAs impacting estrogen receptor ERα expression in breast cancer, we have screened ER-positive breast cancer cells with a library of pre-miRs, and systematically monitored the ERα expression by protein lysate microarrays. There was a significant enrichment of the in silico predicted ERα targeting microRNAs among the hits. The most potent pre-miRs miR-18a/b, miR-193b, miR-206, and miR-302c, were confirmed to directly target ERα and to repress estrogen-responsive genes. The effect of miRNA overexpression on gene expression profile of MCF-7 cells was studied. Furthermore, miR-18a and miR-18b showed increased expression in ERα-negative as compared to ERα-positive clinical tumors. In summary, we present systematic and direct functional and correlative clinical evidence on microRNAs inhibiting ERα signaling in breast cancer.

2009-08-18 | GSE14847 | GEO

H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription

Project description:Hormone-dependent gene expression requires dynamic and coordinated epigenetic changes. Estrogen receptor-positive (ER+) breast cancer is particularly dependent upon extensive chromatin remodeling and changes in histone modifications for the induction of hormone-responsive gene expression. Our previous studies established an important role of bromodomain-containing protein-4 (BRD4) in promoting estrogen-regulated transcription and proliferation of ER+ breast cancer cells. Here, we investigated the association between genome-wide occupancy of histone H4 acetylation at lysine 12 (H4K12ac) and BRD4 in the context of estrogen-induced transcription. Similar to BRD4, we observed that H4K12ac occupancy increases near the transcription start sites (TSS) of estrogen-induced genes as well as at distal ERα binding sites in an estrogen-dependent manner. Interestingly, H4K12ac occupancy highly correlates with BRD4 binding and enhancer RNA production on ERα-positive enhancers. Consistent with an importance in estrogen-induced gene transcription, H4K12ac occupancy globally increased in ER-positive cells relative to ER-negative cells and these levels were further increased by estrogen treatment in an ERα-dependent manner. Together, these findings reveal a strong correlation between H4K12ac and BRD4 occupancy with estrogen-dependent gene transcription and further suggest that modulators of H4K12ac and BRD4 may serve as new therapeutic targets for hormone-dependent cancers. ChIP-seq profiles of H4K12ac in MCF7 cells treated with +/- estrogen treatment and MCF10A cells.

2015-05-02 | E-GEOD-65886 | biostudies-arrayexpress

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