Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA117841 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To better characterize group IE like human breast cancer based on the gene profiles of estrogen actions through estrogen receptor alpha (ER alpha), we identified an ER alpha transcriptional regulatory network for cell cycle in silico. We used two datasets from cell line (Data 1) and clinical samples (Data 2), respectively. Analyses on Data 1 via trajectory clustering and Pathway-Express confirmed the significant estrogen effect on up-regulating cell cycle activities. The gene expression relationships between ER alpha and cell cycle genes were re-identified in Data 2 by three statistical methods – Galton-Pearson’s correlation coefficient, Student’s t-test and the coefficient of intrinsic dependence. They were mostly (56.09%)(46/82) re-confirmed by literature search. E2F1 was found to be the major ER alpha target in regulating cell cycle gene expressions (83.72%)(36/43) via suppressive mode. However, enhanced cell cycle progression via up-regulating some cell cycle genes was predicted in silico possibly involving E2F2, in part. Both tumorigenic and tumor suppressing activities indicated by this network were predicted. This network clearly provides a robust way for uncovering estrogen actions in an ER(+) subtype specific manner.
2009-07-24 | GSE17040 | GEO
Project description:To better characterize group IE like human breast cancer based on the gene profiles of estrogen actions through estrogen receptor alpha (ER alpha), we identified an ER alpha transcriptional regulatory network for cell cycle in silico. We used two datasets from cell line (Data 1) and clinical samples (Data 2), respectively. Analyses on Data 1 via trajectory clustering and Pathway-Express confirmed the significant estrogen effect on up-regulating cell cycle activities. The gene expression relationships between ER alpha and cell cycle genes were re-identified in Data 2 by three statistical methods – Galton-Pearson’s correlation coefficient, Student’s t-test and the coefficient of intrinsic dependence. They were mostly (56.09%)(46/82) re-confirmed by literature search. E2F1 was found to be the major ER alpha target in regulating cell cycle gene expressions (83.72%)(36/43) via suppressive mode. However, enhanced cell cycle progression via up-regulating some cell cycle genes was predicted in silico possibly involving E2F2, in part. Both tumorigenic and tumor suppressing activities indicated by this network were predicted. This network clearly provides a robust way for uncovering estrogen actions in an ER(+) subtype specific manner. Experiment Overall Design: Two clinical datasets were used in this study. One, the 37 clinical arrays (abbreviated as 37A) consist of 26 A for patients positive in estrogen receptor alpha (ER) and in progesterone receptor (PR) immunohistochemical stain (IHC) and 11A for patients negative in ER IHC. This dataset was designated as Data 2. The 31 clinical arrays (31A) consist of 20A for patients positive in ER status but negative in PR status and 11A which are the same as in 37A. This dataset was used for data comparison. All the signals from the mRNA profile of each sample in the experiments were normalized using the internal control RNA- Stratagene's human common reference RNA via statistical method 'rank consistant lowess. Finally, those ratios were transformed by Log2.
2009-08-14 | E-GEOD-17040 | biostudies-arrayexpress
Project description:Retinoic acid receptor-alpha (RAR alpha) is a known estrogen target gene in breast cancer cells. The consequence of RAR alpha induction by estrogen was previously unknown. We now show that RAR alpha is required for efficient estrogen receptor-alpha (ER)-mediated transcription and cell proliferation. RAR alpha can interact with ER-binding sites, but this occurs in an ER-dependent manner, providing a novel role for RAR alpha that is independent of its classic role. We show, on a genome-wide scale, that RAR alpha and ER can co-occupy regulatory regions together within the chromatin. This transcriptionally active co-occupancy and dependency occurs when exposed to the predominant breast cancer hormone, estrogen--an interaction that is promoted by the estrogen-ER induction of RAR alpha. These findings implicate RAR alpha as an essential component of the ER complex, potentially by maintaining ER-cofactor interactions, and suggest that different nuclear receptors can cooperate for effective transcriptional activity in breast cancer cells. RAR alpha silenced breast cancer MCF-7 cell lines or control siRNA in the presence of estrogen or a vehicle. MCF-7 cells were hormone-depleted for 3 d and treated with 100 nM estrogen for 12 h. There were three biological replicates for each of the four different groups.
2010-06-16 | E-GEOD-22213 | biostudies-arrayexpress
Project description:Retinoic acid receptor-alpha (RAR alpha) is a known estrogen target gene in breast cancer cells. The consequence of RAR alpha induction by estrogen was previously unknown. We now show that RAR alpha is required for efficient estrogen receptor-alpha (ER)-mediated transcription and cell proliferation. RAR alpha can interact with ER-binding sites, but this occurs in an ER-dependent manner, providing a novel role for RAR alpha that is independent of its classic role. We show, on a genome-wide scale, that RAR alpha and ER can co-occupy regulatory regions together within the chromatin. This transcriptionally active co-occupancy and dependency occurs when exposed to the predominant breast cancer hormone, estrogen--an interaction that is promoted by the estrogen-ER induction of RAR alpha. These findings implicate RAR alpha as an essential component of the ER complex, potentially by maintaining ER-cofactor interactions, and suggest that different nuclear receptors can cooperate for effective transcriptional activity in breast cancer cells.
2010-06-09 | GSE22213 | GEO
Project description:We report the ER alpha regulatory network of Tamoxifen resistance MCF7 cell line using the Chromatin immunoprecipitated high-throughput sequencing technology (ChIP-seq). By Integrating the gene expression data (previously reported) with the ChIP-seq data, we generated ER alpha regulatory network and pathways. For ER alpha regulatory network, hub TFs with enriched motifs were identified from ER alpha peak together with PolII peaks. We then scan the position weight matrix (PWM) of ER alpha peak region of certain gene to find out the regulatory relationship between hub TF and normal TF. For regulatory pathway, genes were grouped base on their expression value at 4 different time point. Then the hub TF that plays important role in each time point of each group was identified. This study provides a framework for the application of ChIP-seq and gene expression data for the construction of ER alpha regulatory network. 4 different ChIP-seq dataset in Tamoxifen resistance MCF7 cell line
2010-12-20 | E-GEOD-26083 | biostudies-arrayexpress
Project description:Cell-specific transcriptional regulations exerted by the estrogen (E2) receptor alpha (ER) heavily rely upon timely and spatially coordinated processes. We engaged a comparative analysis of such dynamic molecular events at the TFF locus harbouring a cluster of genes co-regulated by E2, in two distinct breast cancer cell lines. Using a combination of methods, we show that the recruitment of ER on cell-specific sites triggers dynamic local modifications of chromatin, which are coordinated in time all along the locus. DNA-FISH experiments further demonstrate that these changes are associated with an E2-dependent reduction in plasticity of this genomic region and are dependent upon cohesin. Importantly, 3C/4C experiments and the use of triplex forming oligonucleotides (TFOs) allowed us to precisely map the three-dimensional network of regulatory events that permits the estrogenic response of this genomic region. These data also evidenced an unexpected functional redundancy of enhancers. Independent duplicate array series, using on one array pooled ChIP triplicates prepared from separate MDA::ER or MCF-7 cell cultures treated with estradiol for 50 minutes.
2014-05-06 | E-GEOD-32132 | biostudies-arrayexpress
Project description:Estrogen Receptor (ER) is a steroid hormone receptor that regulates epithelial genes in breast cancer. ER forms a regulatory network with the other transcription factors, FOXA1 and GATA3. GATA3 is known to be capable of specifying chromatin localization of FOXA1 and ER. GATA3 has been identified as one of the most frequently mutated genes in breast cancer. However, how GATA3 mutations impact this transcriptional network is unknown. Here we investigate the function of one of the recurrent patient-derived GATA3 mutations (R330fs) for this regulatory network. Genomic analysis indicates that the R330fs mutant can disrupt the cooperative action of ER, FOXA1, and GATA3, and induce chromatin relocalization of these factors. Relocalizations of ER and FOXA1 are associated with altered chromatin architectures leading to differential gene expression in the GATA3 mutant cells. These results suggest the active role of GATA3 mutants in ER positive breast tumors.
2020-02-27 | GSE130703 | GEO
Project description:Estrogen receptor-{alpha} (ER{alpha}) and its ligand estradiol play critical roles in breast cancer growth and are important therapeutic targets for this disease. Using chromatin immunoprecipitation (ChIP)-on-chip, ligand-bound ER{alpha} was recently found to function as a master transcriptional regulator via binding to many cis-acting sites genome-wide. Here, we used an alternative technology (ChIP cloning) and identified 94 ER{alpha} target loci in breast cancer cells. The ER{alpha}-binding sites contained both classic estrogen response elements and nonclassic binding sequences, showed specific transcriptional activity in reporter gene assay, and interacted with the key transcriptional regulators, including RNA polymerase II and nuclear receptor coactivator-3. The great majority of the binding sites were located in either introns or far distant to coding regions of genes. Forty-three percent of the genes that lie within 50 kb to an ER{alpha}-binding site were regulated by estradiol. Most of these genes are novel estradiol targets encoding receptors, signaling messengers, and ion binders/transporters. mRNA profiling in estradiol-treated breast cancer cell lines and tissues revealed that these genes are highly ER{alpha} responsive both in vitro and in vivo. Among estradiol-induced genes, Wnt11 was found to increase cell survival by significantly reducing apoptosis in breast cancer cells. Taken together, we showed novel genomic binding sites of ER{alpha} that regulate a novel set of genes in response to estradiol in breast cancer. Our findings suggest that at least a subset of these genes, including Wnt11, may play important in vivo and in vitro biological roles in breast cancer. Experiment Overall Design: This Series currently contains the gene expression data accompanying Zhihong Lin et al. Cancer Research 67,5017-5024(2007). MCF7 cells were treated with vehicle or E2 at a concentration of 10E-9 mol/L for 3 and 6 h. All experiments were performed in triplicate.
2008-06-20 | E-GEOD-11506 | biostudies-arrayexpress
Project description:Breast cancer is a heterogeneous disease and several distinct subtypes exist based on differential gene expression patterns. Molecular apocrine tumours were recently identified as an additional subgroup, characterised as oestrogen receptor negative and androgen receptor positive (ER_ AR+), but with an expression profile resembling ER+ luminal breast cancer. One possible explanation for the apparent incongruity is that ER gene expression programmes could be recapitulated by AR. Using a cell line model of ER_ AR+ molecular apocrine tumours (termed MDA-MB-453 cells), we map global AR binding events and find a binding profile that is similar to ER binding in breast cancer cells. We find that AR binding is a near-perfect subset of FoxA1 binding regions, a level of concordance never previously seen with a nuclear receptor. AR functionality is dependent on FoxA1, since silencing of FoxA1 inhibits AR binding, expression of the majority of the molecular apocrine gene signature and growth cell growth. These findings show that AR binds and regulates ER cis-regulatory elements in molecular apocrine tumours, resulting in a transcriptional programme reminiscent of ER-mediated transcription in luminal breast cancers.
2012-02-18 | E-MTAB-986 | biostudies-arrayexpress
Project description:Estrogen receptor-{alpha} (ER{alpha}) and its ligand estradiol play critical roles in breast cancer growth and are important therapeutic targets for this disease. Using chromatin immunoprecipitation (ChIP)-on-chip, ligand-bound ER{alpha} was recently found to function as a master transcriptional regulator via binding to many cis-acting sites genome-wide. Here, we used an alternative technology (ChIP cloning) and identified 94 ER{alpha} target loci in breast cancer cells. The ER{alpha}-binding sites contained both classic estrogen response elements and nonclassic binding sequences, showed specific transcriptional activity in reporter gene assay, and interacted with the key transcriptional regulators, including RNA polymerase II and nuclear receptor coactivator-3. The great majority of the binding sites were located in either introns or far distant to coding regions of genes. Forty-three percent of the genes that lie within 50 kb to an ER{alpha}-binding site were regulated by estradiol. Most of these genes are novel estradiol targets encoding receptors, signaling messengers, and ion binders/transporters. mRNA profiling in estradiol-treated breast cancer cell lines and tissues revealed that these genes are highly ER{alpha} responsive both in vitro and in vivo. Among estradiol-induced genes, Wnt11 was found to increase cell survival by significantly reducing apoptosis in breast cancer cells. Taken together, we showed novel genomic binding sites of ER{alpha} that regulate a novel set of genes in response to estradiol in breast cancer. Our findings suggest that at least a subset of these genes, including Wnt11, may play important in vivo and in vitro biological roles in breast cancer. Keywords: time course
2008-05-20 | GSE11506 | GEO