Expression data from human breast cancer cells (MCF-7) coexpressing ERalpha and Erbeta, treated with phytoestrogens
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE9936 | GEO | 2008/02/07
SECONDARY ACCESSION(S): PRJNA103937
REPOSITORIES: GEO
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Project description:We used microarrays to detail the global transcriptional response mediated by ERalpha or ERbeta to the phytoestrogen genistein in the MCF-7 human breast cancer cell model. Experiment Overall Design: MCF-7 human breast cancer cells expressing endogenouse Estrogen Receptor Alpha (ERalpha) were infected with adenovirus carrying either estrogen receptor beta (AdERb) or no insert (Ad) at multiplicity of infection (moi) of 20. Cells were then treated with either vehicle control (veh), 6nM 17beta-estradiol (E2), 6nM genistein (LG), 300nM genistein (HG), 300nM S-Equol (EQ), HG+3uM ICI182,780 (IG), EQ+3uM ICI 182,780(IE) for a additional periods of 4h or 24hr before RNA extraction and hybridization on Affymetrix microarrays. We sought to determine if genistein and S-Equol, phytoestrogens selective for the ERbeta can elicit transcriptional response distinctive from those mediated by the ERalpha.
2008-04-10 | E-GEOD-9936 | biostudies-arrayexpress
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
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 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
Project description:This SuperSeries is composed of the following subset Series:; GSE9757: Response to estradiol-ERalpha; GSE9758: Response to estradiol-ERalpha ERE Binding defective mutant; GSE9759: Response to estradiol-Erbeta and estradiol-ERbeta ERE binding defective mutant Experiment Overall Design: Refer to individual Series
2008-06-16 | E-GEOD-9761 | biostudies-arrayexpress
Project description:Estrogens exert many important effects in bone, a tissue that contains both estrogen receptors alpha and beta (ERalpha and ERbeta). To compare the actions of these receptors, we generated U2OS human osteosarcoma cells stably expressing ERalpha or ERbeta, at levels comparable to those in osteoblasts, and we characterized their response to estradiol (E2) over time using Affymetrix GeneChip microarrays to determine the expression of approximately 12,000 genes, followed by quantitative PCR verification of the regulation of selected genes. Of the ca. 100 regulated genes we identified, some were stimulated by E2 equally through ERalpha and ERbeta, whereas others were selectively stimulated via ERalpha or ERbeta. The E2-regulated genes showed three distinct temporal patterns of expression over the 48 h time course studied. Of the functional categories of the E2-regulated genes, most numerous were those encoding cytokines and factors associated with immune response, signal transduction, and cell migration and cytoskeleton regulation, indicating that E2 can exert effects on multiple pathways in these osteoblast-like cell lines. Of note, E2 up-regulated several genes associated with cell motility selectively via ERbeta, in keeping with the selective E2 enhancement of the motility of ERbeta-containing cells. On genes regulated equally by E2 via ERalpha or ERbeta, the phytoestrogen genistein preferentially stimulated gene expression via ERbeta. These studies indicate both common as well as distinct target genes for these two ERs, and identify many novel genes not previously known to be under estrogen regulation. Keywords: other
2004-04-10 | GSE1153 | GEO
Project description:Estrogens exert many important effects in bone, a tissue that contains both estrogen receptors alpha and beta (ERalpha and ERbeta). To compare the actions of these receptors, we generated U2OS human osteosarcoma cells stably expressing ERalpha or ERbeta, at levels comparable to those in osteoblasts, and we characterized their response to estradiol (E2) over time using Affymetrix GeneChip microarrays to determine the expression of approximately 12,000 genes, followed by quantitative PCR verification of the regulation of selected genes. Of the ca. 100 regulated genes we identified, some were stimulated by E2 equally through ERalpha and ERbeta, whereas others were selectively stimulated via ERalpha or ERbeta. The E2-regulated genes showed three distinct temporal patterns of expression over the 48 h time course studied. Of the functional categories of the E2-regulated genes, most numerous were those encoding cytokines and factors associated with immune response, signal transduction, and cell migration and cytoskeleton regulation, indicating that E2 can exert effects on multiple pathways in these osteoblast-like cell lines. Of note, E2 up-regulated several genes associated with cell motility selectively via ERbeta, in keeping with the selective E2 enhancement of the motility of ERbeta-containing cells. On genes regulated equally by E2 via ERalpha or ERbeta, the phytoestrogen genistein preferentially stimulated gene expression via ERbeta. These studies indicate both common as well as distinct target genes for these two ERs, and identify many novel genes not previously known to be under estrogen regulation.
2007-08-03 | E-GEOD-1153 | biostudies-arrayexpress
Project description:Purpose: Endocrine therapies, such as tamoxifen are commonly given to most patients with estrogen receptor (ER) alpha-positive breast carcinoma but are not indicated for persons with ERalpha-negative cancer. The factors responsible for response to tamoxifen in 5-10% of patients with ERalpha-negative tumors are not clear. The aim of the present study was to elucidate the biology and role of the second ER, ERbeta, in patients treated with adjuvant tamoxifen. Experimental Design: We investigated ERbeta by immunohistochemistry in 353 stage II primary breast tumors from patients treated with two years adjuvant tamoxifen, and generated gene expression profiles for a representative subset of 88 tumors. Results: ERbeta was associated with increased survival (distant disease-free survival, P=0.01; overall survival, P=0.22), and in particular within ERalpha-negative patients (P=0.003; P=0.04), but not in the ERalpha-positive subgroup (P=0.49; P=0.88). Lack of ERbeta conferred early relapse (hazard ratio, 14; 95% CI, 1.8-106; P=0.01) within the ERalpha-negative subgroup even after adjustment for other markers. ERalpha was an independent marker only within the ERbeta-negative tumors (hazard ratio, 0.44; 95% CI, 0.21-0.89; P=0.02). An ERbeta gene expression profile was identified and was markedly different from the ERalpha signature. Conclusion: Expression of ERbeta is an independent marker for favorable prognosis after adjuvant tamoxifen treatment in ERalpha-negative breast cancer patients, and involves a gene expression program distinct from ERalpha. These results may be highly clinically significant, because in the U.S. alone, approximately 10,000 women are diagnosed annually with ERalpha-negative/ERbeta-positive breast carcinoma and may benefit from adjuvant tamoxifen. Keywords: Disease state analysis
2007-04-01 | GSE6577 | GEO
Project description:We used ChIP-Seq to map ERalpha binding sites and to profile changes in RNA polymerase II (RNAPII) occupancy in MCF-7 cells in response to estradiol (E2), tamoxifen or fulvestrant. We identified 10,205 high confidence ERalpha binding sites in response to E2 of which 68% contained an estrogen response element (ERE) and only 7% contained a FOXA1 motif. Remarkably, 596 genes already change significantly in RNAPII occupancy (59% up and 41% down) following one hour of E2 exposure. Although pausing of RNA polymerase II occurs frequently in MCF-7 cells (17%) it is only observed on a minority of E2-regulated genes (4%). Tamoxifen and fulvestrant partially reduce ERalpha DNA binding and prevent RNAPII loading on the promoter and coding body on E2-upregulated genes. Both antagonists act differently on E2-downregulated genes. Tamoxifen acts as an agonist, also downregulating these genes while fulvestrant antagonizes E2 induced repression and often increases RNAPII occupancy. Furthermore our data identified genes preferentially regulated by tamoxifen but not by E2 or fulvestrant. Thus, antagonist loaded ERalpha acts mechanistically different on E2-activated and E2-repressed genes.
2009-03-09 | GSE14664 | GEO
Project description:In addition to the estrogen responsive element (ERE)-dependent gene expression, E2-ERbeta regulates transcription through functional interactions with transfactors bound to their cognate regulatory elements on DNA, hence the ERE-independent signaling pathway. However, the relative importance of the ERE-independent pathway in E2-ERbeta signaling is unclear. Our studies in infected ER-negative cell models with an ERbeta mutant (ERbetaDBD) that functions exclusively at the ERE-independent pathway demonstrated that genomic responses assessed by microarrays from the ERE-independent pathway to E2-ERbeta are not sufficient to alter cellular growth, death or motility. These findings suggest that the ERE-dependent pathway is the canonical E2-ERbeta signaling in model cell lines. Keywords: MDA-MB-231 cells
2007-12-04 | GSE9759 | GEO
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.
2011-09-05 | GSE30574 | GEO