Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA280269 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gene expression of the breast cancer cell line T47D-MTVL induced by progestin R5020, in the absense or presence of the JAK/STAT signaling pathway inhibitor AG490. Keywords: Gene expression - T47D-MTVL- hormonal treatment+inhibitors comparison
2007-10-12 | GSE9286 | GEO
Project description:Analysis of the effect of progesterone blockade at the gene expression level. The hypothesis tested in the present study is that elapristone (CDB4124), an antiprogestin, will downregulate genes that are stimulated by R5020, a synthetic progestin, in the T47D breast cancer cell line. Total RNA obtained from T47 breast cancer cells grown for 24 hours in the presence of: 1. The sythetic progestin R5020 compared to vehicle control; 2. The antiprogestin Telapristone (CDB4124) compared to vehicle control; and 3. R5020 compared to R5020 ± Telapristone.
2015-05-15 | E-GEOD-67561 | biostudies-arrayexpress
Project description:Breast cancer cell lines containing the progesterone receptor respond to progestins, altering expression of a subset of genes. In a previously published experiment of inducible knock-down of histone H1 isoforms with an shRNA-expression lentivector (GSE12299), we modified the breast cancer cell line T47D with different vectors. Here, we explored response to progestin R5020 of control cells generated with the empty shRNA-expression vector. Stable breast cancer-derived cell lines containing the empty vector for inducible shRNA expression were grown for two days in the absence of serum. Progestin R5020 or vehicle was added for 6 hours, in duplicate, and RNA was extracted for microarray hybridization.
2013-10-14 | E-GEOD-25077 | biostudies-arrayexpress
Project description:Prolactin and progesterone act together to regulate mammary alveolar development, and both hormones have been implicated in breast cancer initiation and progression. Here we show that Elf5, a prolactin-induced ETS transcription factor that specifies the mammary secretory cell lineage, is also induced by progestins in breast cancer cells via a direct mechanism. To define the transcriptional response to progestin elicited via Elf5 we made an inducible Elf5 sh-RNA knock down model in T47D breast cancer cells and used it to prevent the progestin-induction of Elf5. Functional analysis of Affymetrix gene expression data using Gene Ontologies and Gene Set Enrichment Analysis showed enhancement of the progestin effects on cell cycle gene expression. Cell proliferation assays showed a more efficacious progestin-induced growth arrest when Elf5 was kept at baseline levels. These results showed that progestin-induction of Elf5 expression tempered the anti-proliferative effects of progestins in T47D cells, providing a further mechanistic link between prolactin and progestin in the regulation of mammary cell phenotype.
2010-06-17 | GSE22363 | GEO
Project description:Prolactin and progesterone act together to regulate mammary alveolar development, and both hormones have been implicated in breast cancer initiation and progression. Here we show that Elf5, a prolactin-induced ETS transcription factor that specifies the mammary secretory cell lineage, is also induced by progestins in breast cancer cells via a direct mechanism. To define the transcriptional response to progestin elicited via Elf5 we made an inducible Elf5 sh-RNA knock down model in T47D breast cancer cells and used it to prevent the progestin-induction of Elf5. Functional analysis of Affymetrix gene expression data using Gene Ontologies and Gene Set Enrichment Analysis showed enhancement of the progestin effects on cell cycle gene expression. Cell proliferation assays showed a more efficacious progestin-induced growth arrest when Elf5 was kept at baseline levels. These results showed that progestin-induction of Elf5 expression tempered the anti-proliferative effects of progestins in T47D cells, providing a further mechanistic link between prolactin and progestin in the regulation of mammary cell phenotype. We used Affymetrix expression arrays to determine to what extent Elf5 mediated the transcriptional effects of progestins in T47D cells. We transcript profiled our inducible Elf5 hold-down model using triplicate independent experiments under three conditions: (1) treatment with ethanol vehicle only (Baseline), (2) ORG2058 treatment for 4 days (Pg), and (3) Dox and ORG2058 treatment for 4 days, (Pg-Elf5) designed to prevent the progestin-induction of Elf5 expression.
2010-07-08 | E-GEOD-22363 | biostudies-arrayexpress
Project description:Progesterone receptor (PR) and its co-activators are direct targets of activated cyclin dependent kinases (CDKs) in response to peptide growth factors, progesterone, and deregulation of cell cycle inhibitors. Herein, using the T47D breast cancer model, we probed mechanisms of cell cycle-dependent PR action. In the absence of exogenous progestin, PR is specifically phosphorylated during the G2/M phase. Accordingly, numerous PR target genes are cell cycle regulated, including HSPB8, a heat-shock protein whose high expression is associated with tamoxifen-resistance. Progestin-induced HSPB8 expression required cyclin D1 and was insensitive to anti-estrogens, but blocked by anti-progestins or inhibition of specificity factor 1 (SP1). HSPB8 expression increased with or without ligand when cells were G2/M synchronized or contained high levels of cyclin D1. Knock-down of PR abrogated ligand-independent HSPB8 expression in synchronized cells. Notably, PR and cyclin D1 co-purified in whole cell lysates of transiently transfected COS-1 cells and in PR-positive T47D breast cancer cells expressing endogenous cyclin D1. PR, cyclin D1, and SP1 were recruited to the HSPB8 promoter in progestin-treated T47D breast cancer cells. Mutation of PR Ser345 to Ala (S345A) or inhibition of CDK2 activity using roscovitine disrupted PR/cyclin D1 interactions with DNA and blocked HSPB8 mRNA expression. Interaction of phosphorylated PRs with SP1 and cyclin D1 provides a mechanism for targeting transcriptionally active PRs to selected gene promoters relevant to breast cancer progression. Understanding the functional linkage between PR and cell cycle regulatory proteins will provide keys to targeting novel PR/cyclin D1 cross-talk in both hormone-responsive and HSPB8-high refractory disease. The study contains 4 different sample groups measured in triplicate, for a total of 12 individual samples (12 arrays). In T47D human breast cancer cell lines stably expressing PR-B, cells were synchronized (or not synchronized) before G2/M phase using nocodazole. These cell lines (synchronized or not synchronized) were treated with either (1) vehicle control (ethanol) or (2) PR ligand R5020 10e-8 M for 6 hours before total RNA harvest. Thus, the experiment contains two cell lines, and two treatments (4 sample groups) treated and analyzed in triplicate (12 microarrays). Standard Illumina HT-12v4 chip controls were used during hybridization.
2014-02-27 | E-GEOD-46715 | biostudies-arrayexpress
Project description:The progesterone receptor (PR) and its coactivators are direct targets of activated cyclin-dependent kinases (CDKs) in response to peptide growth factors, progesterone, and deregulation of cell cycle inhibitors. Herein, using the T47D breast cancer model, we probed mechanisms of cell cycle-dependent PR action. In the absence of exogenous progestin, the PR is specifically phosphorylated during the G2/M phase. Accordingly, numerous PR target genes are cell cycle regulated, including HSPB8, a heat-shock protein whose high expression is associated with tamoxifen resistance. Progestin-induced HSPB8 expression required cyclin D1 and was insensitive to antiestrogens but blocked by antiprogestins or inhibition of specificity factor 1 (SP1). HSPB8 expression increased with or without ligand when cells were G2/M synchronized or contained high levels of cyclin D1. Knockdown of PRs abrogated ligand-independent HSPB8 expression in synchronized cells. Notably, PRs and cyclin D1 copurified in whole-cell lysates of transiently transfected COS-1 cells and in PR-positive T47D breast cancer cells expressing endogenous cyclin D1. PRs, cyclin D1, and SP1 were recruited to the HSPB8 promoter in progestin-treated T47D breast cancer cells. Mutation of PR Ser345 to Ala (S345A) or inhibition of CDK2 activity using roscovitine disrupted PR/cyclin D1 interactions with DNA and blocked HSPB8 mRNA expression. Interaction of phosphorylated PRs with SP1 and cyclin D1 provides a mechanism for targeting transcriptionally active PRs to selected gene promoters relevant to breast cancer progression. Understanding the functional linkage between PRs and cell cycle regulatory proteins will provide keys to targeting novel PR/cyclin D1 cross talk in both hormone-responsive disease and HSPB8-high refractory disease with high HSPB8 expression.
2014-02-27 | GSE46715 | GEO
Project description:Breast cancer cell lines containing the progesterone receptor respond to progestins, altering expression of a subset of genes. In a previously published experiment of inducible knock-down of histone H1 isoforms with an shRNA-expression lentivector (GSE12299), we modified the breast cancer cell line T47D with different vectors. Here, we explored response to progestin R5020 of control cells generated with the empty shRNA-expression vector.
2013-10-14 | GSE25077 | GEO
Project description:Analysis of the effect of progesterone blockade at the gene expression level. The hypothesis tested in the present study is that elapristone (CDB4124), an antiprogestin, will downregulate genes that are stimulated by R5020, a synthetic progestin, in the T47D breast cancer cell line.
2015-05-15 | GSE67561 | 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