E-GEOD-24592
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA132379
PROVIDER: E-GEOD-24592 | ExpressionAtlas | 2015-08-12
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:Genomic Collaboration of Estrogen Receptor-α and ERK2 in Regulating Gene and Proliferation Programs
| PRJNA132379 | ENA
Project description:The closely related transcription factors (TFs), estrogen receptors ER? and ER?, regulate divergent gene expression programs and proliferative outcomes in breast cancer. Utilizing MCF-7 breast cancer cells with ER?, ER?, or both receptors as a model system to define the basis of differing response specification by related TFs, we show that these TFs and their key coregulators, SRC3 and RIP140, generate overlapping as well as unique chromatin-binding and transcription-regulating modules. Cistrome and transcriptome analyses and use of clustering algorithms delineated 11 clusters representing different chromatin-bound receptor and coregulator assemblies that could be functionally associated through enrichment analysis with distinct patterns of gene regulation and preferential coregulator usage, RIP140 with ER? and SRC3 with ER?. The receptors modified each other’s transcriptional effect, and ER? countered the proliferative drive of ER? through several novel mechanisms associated with specific binding site clusters. Our findings delineate distinct TF-coregulator assemblies that function as control nodes specifying precise patterns of gene regulation, proliferation, and metabolism, as exemplified by two of the most important nuclear hormone receptors in human breast cancer. Examination of Estrogen Receptors alpha and beta and their coregulators SRC3 and RIP140 in different cell types
2013-07-05 | E-GEOD-42348 | biostudies-arrayexpress
Project description:Estrogen receptor alpha (ERalpha) is a ligand-dependent transcription factor that plays an important role in breast cancer. Estrogen-dependent gene regulation by ERalpha can be mediated by interaction with other DNA-binding proteins, such as activator protein-1 (AP-1). The nature of such interactions in mediating the estrogen response in breast cancer cells remains unclear. Here we show that knockdown of c-Fos, a component of the transcription factor AP-1, attenuates the expression of 37% of all estrogen-regulated genes, suggesting that AP-1 is a fundamental factor for ERalpha-mediated transcription. Additionally, knockdown of c-Fos affected the expression of a number of genes that were not regulated by estrogen. Pathway analysis reveals that silencing of c-Fos downregulates an E2F1-dependent pro-proliferative gene network. Thus, modulation of the E2F1 pathway by c-Fos represents a novel mechanism by which c-Fos enhances breast cancer cell proliferation. Furthermore, we show that c-Fos and ERalpha can cooperate in regulating E2F1 gene expression by binding to regulatory elements in the E2F1 promoter. To start to dissect the molecular details of the cross-talk between AP-1 and estrogen signaling, we identify a novel ERalpha/AP-1 target, PKIB (cAMP-dependent protein kinase inhibitor-beta), which is overexpressed in ERalpha-positive breast cancer tissues. Knockdown of PKIB by siRNA results in drastic growth suppression of breast cancer cells. Collectively, our findings support AP-1 as a critical factor that governs estrogen-dependent gene expression and breast cancer proliferation programs. MCF-7 cells were transfected with a control siRNA or with the pool of siRNAs targeting c-Fos for 72 h and were then treated with vehicle or E2 for 24 h, and global gene expression profiles were assessed. Three or four biological replicates were used for each group.
2012-08-05 | E-GEOD-36586 | 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: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.
2010-06-09 | GSE22213 | GEO
Project description:Estrogen receptor α (ERα) is the major driving transcription factor in normal mammary gland development as well as breast cancer initiation and progression.However,the fundamental mechanisms,including global cistromic and genomic transcriptional responses that are required to elicit mammary epithelial cell proliferation in response to ERα, have not been elucidated. We used chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) to identify estrogen regulated genes that directly recruit ERα in the WT mouse mammary gland
2019-07-23 | GSE129847 | GEO
Project description:JNK1 ChIP-chip and ER-alpha ChIP-chip were performed on NimbleGen genomic tiling arrays to understand the genomic binding patterns of this MAP kinase and receptor and their relationship to gene expression. ChIP-chip analysis of JNK1 occupancy at promoters before and after estrogen treatment. 2 biological replicates (rep1 and rep2, rep3A and rep3B), 2 technical replicates each. ChIP-chip analysis of ER-alpha occupancy at promoters before and after estrogen treatment. 2 biological replicates, 2 technical replicates for one of the replicates (1 and 2).
2012-03-31 | E-GEOD-13200 | biostudies-arrayexpress
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:Estrogen receptor alpha (ERalpha) is a ligand-dependent transcription factor that plays an important role in breast cancer. Estrogen-dependent gene regulation by ERalpha can be mediated by interaction with other DNA-binding proteins, such as activator protein-1 (AP-1). The nature of such interactions in mediating the estrogen response in breast cancer cells remains unclear. Here we show that knockdown of c-Fos, a component of the transcription factor AP-1, attenuates the expression of 37% of all estrogen-regulated genes, suggesting that AP-1 is a fundamental factor for ERalpha-mediated transcription. Additionally, knockdown of c-Fos affected the expression of a number of genes that were not regulated by estrogen. Pathway analysis reveals that silencing of c-Fos downregulates an E2F1-dependent pro-proliferative gene network. Thus, modulation of the E2F1 pathway by c-Fos represents a novel mechanism by which c-Fos enhances breast cancer cell proliferation. Furthermore, we show that c-Fos and ERalpha can cooperate in regulating E2F1 gene expression by binding to regulatory elements in the E2F1 promoter. To start to dissect the molecular details of the cross-talk between AP-1 and estrogen signaling, we identify a novel ERalpha/AP-1 target, PKIB (cAMP-dependent protein kinase inhibitor-beta), which is overexpressed in ERalpha-positive breast cancer tissues. Knockdown of PKIB by siRNA results in drastic growth suppression of breast cancer cells. Collectively, our findings support AP-1 as a critical factor that governs estrogen-dependent gene expression and breast cancer proliferation programs.
2012-08-06 | GSE36586 | GEO