Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Novel estrogen-responsive genes (ERGs) for the evaluation of estrogenic activity

ABSTRACT: Estrogen action is mediated by various genes including estrogen-responsive genes (ERGs). ERGs have been used as markers for gene expression and as reporter-genes, while gene expression profiling using a set of ERGs has been used as statistically reliable transcriptomic assays, such as DNA microarray assays and RNA-seq. However, the quality of ERGs has not been extensively examined. Here, we found a set of 300 ERGs newly identified by six sets of RNA-seq data obtained from estrogen-treated and control human breast cancer MCF-7 cells. The ERGs exhibited statistical stability as judged by the coefficient of variation (CV) analysis, and their usefulness as markers for estrogenic activity by examining the stability of data in the study of correlation analysis, and functional association with estrogen action through database searches. A set of the top 30 genes based on CV ranking were further evaluated quantitatively by RT-PCR and qualitatively by a functional analysis using GO and KEGG databases and by a mechanistic analysis to classify ERα/β-dependent or ER-independent types of transcriptional regulation. The 30 ERGs were characterized by (1) the enzymes, such as metabolic enzymes, proteases and protein kinases, (2) the genes with specific cell functions, such as cell-signaling mediators, tumor-suppressors and the roles in breast cancer, (3) the association with transcriptional regulation, and/or (4) estrogen-responsiveness. Therefore, the ERGs identified here could represent various cell functions and cell signaling pathways including estrogen signaling, and thus, would be useful to evaluate estrogenic activity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE205784 | GEO | 2022/08/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Breast Cancer Therapies Reduce Risk of Alzheimer’s Disease and Promote Estrogenic Pathways and Action in Brain

Project description:Worldwide an ever-increasing number of women are prescribed estrogen modulating therapies (EMTs) for the treatment of breast cancer. In parallel, aging of the global population of women will contribute to risk of both breast cancer and Alzheimer’s disease. To address the impact of anti-estrogen therapies on risk of Alzheimer’s and neural function, we conducted medical informatic and molecular pharmacology analyses to determine the impact of EMTs on risk of Alzheimer’s followed by determination of EMT estrogenic mechanisms of action in neurons. In a propensity matched data set of 260,232 women with breast cancer, medical informatic analyses indicated that EMTs were associated with reduced risk of AD which was driven by patients receiving tamoxifen or aromatase inhibitors whereas raloxifene was ineffective independently validating earlier reports. Mechanistically, a comparative analysis of EMTs vs estradiol was conducted to determine whether EMTs exerted estrogenic action in neural cells in-vitro and in brain in-vivo. Outcomes of mechanistic analyses indicated that select EMTs induced estrogenic action and pathways in neural cells including promoting neuronal morphological plasticity, electrophysiological indicators of synaptic connectivity, mitochondrial number and function and induction of transcriptomic pathways consistent with estrogenic outcomes. Collectively, these data provide both clinical and mechanistic data indicating that select EMTs exert estrogenic agonist action in neural tissue that are associated with reduced risk of Alzheimer’s disease while simultaneously acting as effective estrogen receptor antagonists in breast.

2023-11-01 | GSE241054 | GEO

Estrogenic activity of fermented soymilk extracts and soy compounds

Project description:To understand the complex mechanism of estrogen action, multiple assays based on different biological principles is important. Here, multiple assays based on cell, protein and transcription assays were used to evaluate estrogenic activity of soymilk extracts before and after fermentation, and four soy compounds, genistein and daidzein, and their glycosides, genistin and daidzin, respectively. The data obtained by a transcription assay, RNA-sequencing (RNA-seq), was further examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis to understand cell functions, i.e. biological processes and metabolic pathways. Among the cell functions identified, the sets of genes for cell division/cell cycle and DNA replication/DNA repair are significantly up-regulated, whereas those for autophagy are significantly down-regulated, which explains well the enhanced activity of cell proliferation by these materials. The applications of estrogenic activity of soymilk extracts and soy flavonoids, and the contribution of fermentation, include pharmacological benefits, such as bone protection/bone regeneration, cancer chemoprevention, neuroprotection and the treatment of menopausal syndromes.

2023-10-31 | GSE226627 | GEO

Developmental Reprogramming of Myometrial Stem Cells by Endocrine Disruptor Linking to Risk of Uterine Fibroids [RRBS]

Project description:We report that developmental exposure to the endocrine disrupting chemical (EDC) diethylstilbestrol increases the estrogen action in myometrial stem cells (MMSCs), the origin from which UFs originate. The expression of reprogrammed estrogen responsive genes (ERGs) is driven by activated mixed lineage leukemia protein-1 (MLL1) in MMSCs. Deactivation of MLL1 reverses reprogramming of ERG expression. In addition, upregulation of ERGs occurs via DNA hypomethylation mechanism. Furthermore, the secretome of reprogrammed MMSCs enhances the proliferation of differentiated myometrial cells through activation of β-catenin signaling. This work identifies epigenetic mechanisms of MLL1/DNA methyltransferase- mediated MMSC reprogramming, and EDC exposure epigenetically targets MMSCs and imparts a hormonal imprint on the ERGs resulting in a “hyper-estrogenized” phenotype and increased hormone-dependent risk of UFs.

2023-08-07 | GSE157502 | GEO

Developmental Reprogramming of Myometrial Stem Cells by Endocrine Disruptor Linking to Risk of Uterine Fibroids [RNA-Seq]

2023-08-07 | GSE157500 | GEO

Developmental Reprogramming of Myometrial Stem Cells by Endocrine Disruptor Linking to Risk of Uterine Fibroids [ChIP-Seq]

Project description:We report that developmental exposure to the endocrine disrupting chemical (EDC) diethylstilbestrol increases the estrogen action in myometrial stem cells (MMSCs), the origin from which UFs originate. The expression of reprogrammed estrogen responsive genes (ERGs) is driven by activated mixed lineage leukemia protein-1 (MLL1) in MMSCs. Deactivation of MLL1 reverses reprogramming of ERG expression. In addition, upregulation of ERGs occurs via DNA hypomethylation mechanism. Furthermore, the secretome of reprogrammed MMSCs enhances the proliferation of differentiated myometrial cells through activation of β-catenin signaling. This work identifies epigenetic mechanisms of MLL1/DNA methyltransferase- mediated MMSC reprogramming, and EDC exposure epigenetically targets MMSCs and imparts a hormonal imprint on the ERGs resulting in a "hyper-estrogenized" phenotype and increased hormone-dependent risk of UFs.

2023-08-07 | GSE157498 | GEO

Use of toxicogenomics for screening of estrogenic activity

Project description:Due to its high throughput nature, toxicogenomics can provide a broad picture of a toxic response, offering the ideal functional platform for grouping chemicals according to mechanistic similarity. In this way, toxicogenomics has found its way into predictive toxicology. However, so far, the predictive potential of toxicogenomics in an endocrine disruptive screening context has not been extensively examined. The aim of this study was to combine a toxicogenomics approach with an estrogen-sensitive MCF-7 cell system. In total, 18 compounds with endocrine disruptive potential were selected, of which 11 are listed as ICCVAM reference compounds for validation of estrogen receptor (ER) binding and transactivation assays. In this way, the grouping and classification potential of the gene expression profiles could be directly compared to the more classical estrogenicity screens, such as ER binding, ER transactivation and MCF-7 cell proliferation assays. Results indicated that this toxicogenomics approach was clearly capable of grouping compounds into strong, weak and non estrogenic groups. This demonstrates the value of toxicogenomics for evaluating gradual differences in related modes of action, in addition to the more common search for opposite modes of action. The chemical groups were represented by interesting marker genes such as PGR, ERBB2, CXCL12, AREG and EGR3, including some early-responsive (4h) potential biomarkers. These results open the discussion on the added value of a broader endpoint evaluation in estrogenicity screens provided by omics-techniques compared to the classical single endpoint based assays.

2015-10-01 | GSE16881 | GEO

Transcriptomic analysis of the estrogenic effect of soy protein isolate in rat uterus

Project description:There are concerns regarding possible reproductive toxicity from consumption of soy including an increased risk of endometriosis and endometrial cancer. We used global uterine gene expression profiles in adult ovariectomized (OVX) female rats assessed by RNAseq to examine the estrogenicity of soy protein isolate (SPI) and the potential for feeding SPI to alter estrogen signaling in the uterus. Rats were fed AIN93G diets made with casein (CAS) or SPI from postnatal day (PND) 30. Rats were OVX on PND 50 and infused with 17 beta-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05) and significantly altered expression of 2084 uterine genes. In contrast, SPI feeding had no effect on uterine weight and only altered expression of 177 genes. Overlap between E2 and SPI genes was limited to 69 genes (3%). GO analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of ER alpha to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were cancer pathways and extracellular organization. SPI feeding up-regulated uterine PPAR signaling and fatty acid metabolism. The combination of E2 and SPI feeding resulted in significant regulation of 715 fewer genes relative to E2 alone. In a separate experiment, the combination of E2 and SPI reversed the ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA). These data suggest SPI does not act as a weak estrogen in the uterus but appears to be a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and to be anti-estrogenic in the presence of endogenous estrogens. Rat uterus mRNA of ovariectomized adult female rats subject to four different diets (Caseine, Caseine + E2, Soy and Soy+E2 ) were sequenced, in triplicate, in an Illumina GAIIx sequencer.

2015-06-13 | E-GEOD-69819 | biostudies-arrayexpress

Transcriptomic analysis of the estrogenic effect of soy protein isolate in rat uterus

2015-06-13 | GSE69819 | GEO

Gene expression signature involved in estrogen receptor status and prognosis of breast cancers.

Project description:Fine needle aspiration biopsies (FNABs) of breast cancers were taken before and after surgeries from 16 patients. The cDNA microarray data were used to determine the gene expression profile responding to patient's clinical finding and tumor's pathological changes. A gene profile was generated as Estrogen Receptor Gene Signature (ERGS). The ERGS was verified in a reference dataset and correlated with patient's prognosis significantly. Keywords: Breast cancer, fine needle biopsy, estrogen receptor, prognostic gene signature

2009-07-01 | GSE12080 | GEO

Gene expression signature involved in estrogen receptor status and prognosis of breast cancers.

2009-07-01 | E-GEOD-12080 | biostudies-arrayexpress