Hyperactivation of PI3K promotes escape from hormone dependence in estrogen receptor-positive breast cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE19639 | GEO | 2010/06/15
SECONDARY ACCESSION(S): PRJNA122527
REPOSITORIES: GEO
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Project description:Hyperactivation of phosphatidylinositol-3 kinase (PI3K) promotes escape from hormone dependence in estrogen receptor-positive breast cancer. A significant fraction of breast cancers exhibit de novo or acquired resistance to estrogen deprivation. We used gene expression microarrays to identify genes and pathways that are commonly dysregulated in ER+ cell lines with acquired hormone-independent growth. MCF-7, ZR75-1, MDA-361, and HCC-1428 ER+, estrogen-responsive breast cancer cells were cultured under hormone-depleted conditions (10% DCC-FBS) for several months until sustainable hormone-independent cell populations emerged. Parental and long-term estrogen-deprived (LTED) cells were treated with 10% dextran-coated charcoal-treated fetal bovine serum (DCC-FBS) x 24 hrs prior to RNA harvest for array analysis.
2010-06-23 | E-GEOD-19639 | biostudies-arrayexpress
Project description:A significant fraction of breast cancers exhibit de novo or acquired resistance to estrogen deprivation. To model resistance to aromatase inhibitor (AI) therapy, long-term estrogen-deprived (LTED) derivatives of MCF-7 and HCC-1428 cells were generated through culture for 3 and 7 months under hormone-depleted conditions, respectively. These LTED cells showed sensitivity to the ER downregulator fulvestrant under hormone-depleted conditions, suggesting continued dependence upon ER signaling for hormone-independent growth. To evaluate the role of ER in hormone-independent growth, LTED cells were treated +/- 1 uM fulvestrant x 48 h before RNA was harvested for gene expression analysis. MCF-7/LTED and HCC-1428/LTED cells were treated with 10% DCC-FBS with or without the estrogen receptor antagonist drug fulvestrant for 48 hrs prior to RNA harvest for array analysis. Three replicates per condition.
2012-05-13 | E-GEOD-22533 | biostudies-arrayexpress
Project description:A significant fraction of breast cancers exhibit de novo or acquired resistance to estrogen deprivation. To model resistance to aromatase inhibitor (AI) therapy, long-term estrogen-deprived (LTED) derivatives of MCF-7 and HCC-1428 cells were generated through culture for 3 and 7 months under hormone-depleted conditions, respectively. These LTED cells showed sensitivity to the ER downregulator fulvestrant under hormone-depleted conditions, suggesting continued dependence upon ER signaling for hormone-independent growth. To evaluate the role of ER in hormone-independent growth, LTED cells were treated +/- 1 uM fulvestrant x 48 h before RNA was harvested for gene expression analysis.
2012-05-14 | GSE22533 | GEO
Project description:Hormone-independent breast cancer cells (MCF-7/LTED and HCC-1428/LTED) were analyzed by ChIP-seq for estrogen receptor a to identify ER-DNA binding events that occur in the absence of estrogens.
2012-02-10 | GSE27300 | GEO
Project description:Transcriptomic changes and estrogen and progesterone receptor binding in multiple ER+/PR+ models (eight ER+/PR+ patient tumors, various T47Ds, ZR75) and multiple ER+/PR-negative models (four ER+/PR- patient tuumors, PR-deficient T47D and MCF7 cells) treated with various hormone combinations. Results: In isolation, estrogen and progestin act as genomic agonists by regulating the expression of common target genes in similar directions, but at different levels. Similarly, in isolation, progestin is also a weak phenotypic agonist of estrogen action. However, in the presence of both hormones, progestin behaves as a phenotypic estrogen antagonist. PR remodels nucleosomes to noncompetitively redirect ER genomic binding to distal enhancers enriched for BRCA1 binding motifs and sites that link PR and ER/PR complexes. Importantly, when both hormones are present, progestin modulates estrogen action such that responsive transcriptomes, cellular processes and ER/PR recruitment to genomic sites correlate with those observed with PR alone, but not ER alone. Conclusions: Genomic Agonism and Phenotypic Antagonism between Estrogen and Progesterone Receptors in Breast Cancer. Individual and concerted actions of ER and PR highlight the prognostic and therapeutic value of PR in ER+/PR+ breast cancers. ER+/PR+ and ER+/PR-deficient model systems were deprived of steroids by culturing them in phenol red free RPMI 1640 media that is supplemented with 10% charcoal-stripped fetal bovine serum and 1% penicillin/streptomycin. Subsequently, these steroid-deprived models were treated with either vehicle, 10 nM estradiol, 10 nM progestin R5020 or 10 nM of both the hormones and genomics (ChIP-seq and RNA-seq) was performed. ChIP-seq was done after 45 minutes of hormone treatments. For cell models, RNA-seq was done after 12 hours of hormone treatments. Tumor explants were treated with either 24 or 48 hours.
2016-06-01 | E-GEOD-80367 | biostudies-arrayexpress
Project description:Transcriptomic changes and estrogen and progesterone receptor binding in multiple ER+/PR+ models (eight ER+/PR+ patient tumors, various T47Ds, ZR75) and multiple ER+/PR-negative models (four ER+/PR- patient tuumors, PR-deficient T47D and MCF7 cells) treated with various hormone combinations. Results: In isolation, estrogen and progestin act as genomic agonists by regulating the expression of common target genes in similar directions, but at different levels. Similarly, in isolation, progestin is also a weak phenotypic agonist of estrogen action. However, in the presence of both hormones, progestin behaves as a phenotypic estrogen antagonist. PR remodels nucleosomes to noncompetitively redirect ER genomic binding to distal enhancers enriched for BRCA1 binding motifs and sites that link PR and ER/PR complexes. Importantly, when both hormones are present, progestin modulates estrogen action such that responsive transcriptomes, cellular processes and ER/PR recruitment to genomic sites correlate with those observed with PR alone, but not ER alone. Conclusions: Genomic Agonism and Phenotypic Antagonism between Estrogen and Progesterone Receptors in Breast Cancer. Individual and concerted actions of ER and PR highlight the prognostic and therapeutic value of PR in ER+/PR+ breast cancers. ER+/PR+ and ER+/PR-deficient model systems were deprived of steroids by culturing them in phenol red free RPMI 1640 media that is supplemented with 10% charcoal-stripped fetal bovine serum and 1% penicillin/streptomycin. Subsequently, these steroid-deprived models were treated with either vehicle, 10 nM estradiol, 10 nM progestin R5020 or 10 nM of both the hormones and genomics (ChIP-seq and RNA-seq) was performed. ChIP-seq was done after 45 minutes of hormone treatments. For cell models, RNA-seq was done after 12 hours of hormone treatments. Tumor explants were treated with either 24 or 48 hours.
2016-06-01 | E-GEOD-80365 | biostudies-arrayexpress
Project description:Transcriptomic changes and estrogen and progesterone receptor binding in multiple ER+/PR+ models (eight ER+/PR+ patient tumors, various T47Ds, ZR75) and multiple ER+/PR-negative models (four ER+/PR- patient tuumors, PR-deficient T47D and MCF7 cells) treated with various hormone combinations. Results: In isolation, estrogen and progestin act as genomic agonists by regulating the expression of common target genes in similar directions, but at different levels. Similarly, in isolation, progestin is also a weak phenotypic agonist of estrogen action. However, in the presence of both hormones, progestin behaves as a phenotypic estrogen antagonist. PR remodels nucleosomes to noncompetitively redirect ER genomic binding to distal enhancers enriched for BRCA1 binding motifs and sites that link PR and ER/PR complexes. Importantly, when both hormones are present, progestin modulates estrogen action such that responsive transcriptomes, cellular processes and ER/PR recruitment to genomic sites correlate with those observed with PR alone, but not ER alone. Conclusions: Genomic Agonism and Phenotypic Antagonism between Estrogen and Progesterone Receptors in Breast Cancer. Individual and concerted actions of ER and PR highlight the prognostic and therapeutic value of PR in ER+/PR+ breast cancers. ER+/PR+ and ER+/PR-deficient model systems were deprived of steroids by culturing them in phenol red free RPMI 1640 media that is supplemented with 10% charcoal-stripped fetal bovine serum and 1% penicillin/streptomycin. Subsequently, these steroid-deprived models were treated with either vehicle, 10 nM estradiol, 10 nM progestin R5020 or 10 nM of both the hormones and genomics (ChIP-seq and RNA-seq) was performed. ChIP-seq was done after 45 minutes of hormone treatments. For cell models, RNA-seq was done after 12 hours of hormone treatments. Tumor explants were treated with either 24 or 48 hours.
2016-06-01 | E-GEOD-80366 | biostudies-arrayexpress
Project description:Transcriptomic changes and estrogen and progesterone receptor binding in multiple ER+/PR+ models (eight ER+/PR+ patient tumors, various T47Ds, ZR75) and multiple ER+/PR-negative models (four ER+/PR- patient tuumors, PR-deficient T47D and MCF7 cells) treated with various hormone combinations. Results: In isolation, estrogen and progestin act as genomic agonists by regulating the expression of common target genes in similar directions, but at different levels. Similarly, in isolation, progestin is also a weak phenotypic agonist of estrogen action. However, in the presence of both hormones, progestin behaves as a phenotypic estrogen antagonist. PR remodels nucleosomes to noncompetitively redirect ER genomic binding to distal enhancers enriched for BRCA1 binding motifs and sites that link PR and ER/PR complexes. Importantly, when both hormones are present, progestin modulates estrogen action such that responsive transcriptomes, cellular processes and ER/PR recruitment to genomic sites correlate with those observed with PR alone, but not ER alone. Conclusions: Genomic Agonism and Phenotypic Antagonism between Estrogen and Progesterone Receptors in Breast Cancer. Individual and concerted actions of ER and PR highlight the prognostic and therapeutic value of PR in ER+/PR+ breast cancers.
2016-06-01 | GSE80367 | GEO
Project description:Transcriptomic changes and estrogen and progesterone receptor binding in multiple ER+/PR+ models (eight ER+/PR+ patient tumors, various T47Ds, ZR75) and multiple ER+/PR-negative models (four ER+/PR- patient tuumors, PR-deficient T47D and MCF7 cells) treated with various hormone combinations. Results: In isolation, estrogen and progestin act as genomic agonists by regulating the expression of common target genes in similar directions, but at different levels. Similarly, in isolation, progestin is also a weak phenotypic agonist of estrogen action. However, in the presence of both hormones, progestin behaves as a phenotypic estrogen antagonist. PR remodels nucleosomes to noncompetitively redirect ER genomic binding to distal enhancers enriched for BRCA1 binding motifs and sites that link PR and ER/PR complexes. Importantly, when both hormones are present, progestin modulates estrogen action such that responsive transcriptomes, cellular processes and ER/PR recruitment to genomic sites correlate with those observed with PR alone, but not ER alone. Conclusions: Genomic Agonism and Phenotypic Antagonism between Estrogen and Progesterone Receptors in Breast Cancer. Individual and concerted actions of ER and PR highlight the prognostic and therapeutic value of PR in ER+/PR+ breast cancers.
2016-06-01 | GSE80366 | GEO
Project description:Transcriptomic changes and estrogen and progesterone receptor binding in multiple ER+/PR+ models (eight ER+/PR+ patient tumors, various T47Ds, ZR75) and multiple ER+/PR-negative models (four ER+/PR- patient tuumors, PR-deficient T47D and MCF7 cells) treated with various hormone combinations. Results: In isolation, estrogen and progestin act as genomic agonists by regulating the expression of common target genes in similar directions, but at different levels. Similarly, in isolation, progestin is also a weak phenotypic agonist of estrogen action. However, in the presence of both hormones, progestin behaves as a phenotypic estrogen antagonist. PR remodels nucleosomes to noncompetitively redirect ER genomic binding to distal enhancers enriched for BRCA1 binding motifs and sites that link PR and ER/PR complexes. Importantly, when both hormones are present, progestin modulates estrogen action such that responsive transcriptomes, cellular processes and ER/PR recruitment to genomic sites correlate with those observed with PR alone, but not ER alone. Conclusions: Genomic Agonism and Phenotypic Antagonism between Estrogen and Progesterone Receptors in Breast Cancer. Individual and concerted actions of ER and PR highlight the prognostic and therapeutic value of PR in ER+/PR+ breast cancers.
2016-06-01 | GSE80365 | GEO