Gene expression in response to progestin R5020
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE25077 | GEO | 2013/10/14
SECONDARY ACCESSION(S): PRJNA134745
REPOSITORIES: GEO
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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: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: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: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: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: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:Although non-genomic steroid receptor pathways have been studied over the past decade, little is known about the direct gene expression changes that take place as a consequence of their activation. Progesterone controls proliferation of rat endometrial stromal cells during the peri-implantation phase of pregnancy. We showed that picomolar concentration of progestin R5020 mimics this control in UIII endometrial stromal cells via ERK1-2 and AKT activation mediated by interaction of Progesterone Receptor (PR) with Estrogen Receptor beta (ERb) and without transcriptional activity of endogenous PR and ER. Here we identify early downstream targets of cytoplasmic PR signaling and their possible role in endometrial stromal cell proliferation. Microarray analysis of global gene expression changes in UIII cells treated for 45 min with progestin identified 97 up- and 341 down-regulated genes. The most over-represented molecular functions were transcription factors and regulatory factors associated with cell proliferation and cell cycle, a large fraction of which were repressors down-regulated by hormone. Further analysis verified that progestins regulate Ccnd1, JunD, Usf1, Gfi1, Cyr61, and Cdkn1b through PR-mediated activation of ligand-free ER, ERK1-2 or AKT, in the absence of genomic PR binding. ChIP experiments show that progestin promoted the interaction of USF1 with the proximal promoter of the Cdc2 gene, and Usf1 knockdown abrogated Cdc2 progestin-dependent transcriptional regulation providing a mechanism for direct regulation of its expression. Finally, Cdc2 knockdown blocked R5020 induced UIII cell proliferation. We conclude that progestin induced proliferation of endometrial stromal cells requires ERK1-2 and AKT mediated early regulation of USF1, that induces Cdc2. To our knowledge, this is the first description of early target genes of progestin-activated classical PR via crosstalk with protein kinases and independently of hormone receptor binding to the genomic targets.
2015-03-06 | GSE55992 | GEO
Project description:Elucidating the global function of a transcription factor implies the identification of its target genes and genomic binding sites. The role of chromatin in this context is unclear, but the dominant view is that factors bind preferentially to nucleosome-depleted regions, identified as DNaseI-hypersensitive sites (DHS). Here we show by chromatin-IP, MNase and DNaseI assays followed by deep sequencing that the progesterone receptor (PR) requires nucleosomes for optimal binding and function. In breast cancer cells treated with progestins we identified 25,000 PR binding sites (PRbs), the majority encompassing several copies of the hexanucleotide TGTYCY, highly abundant in the genome. We found that functional PRbs accumulate around progesterone-induced genes mainly in enhancers, are enriched in DHS but exhibit high nucleosome occupancy. Progestin stimulation results in remodeling of these nucleosomes with displacement of histones H1 and H2A/H2B dimers. Our results strongly suggest that nucleosomes are crucial for PR binding and hormonal gene regulation. T47D-MTVL human breast cancer cells were incubated with the progestin R5020 for different times between 0 to 360 minutes at 37ºC. ChIP-seq experiments were performed using antibodies against progesterone receptor and a single Sample each with anti-H3K4me3 and anti-H3K4me1. Mononucleosomal DNA was prepared from cells untreated or stimulated 60 min with R5020 and subjected to deep sequencing using the Solexa Genome Analyzer.
2012-12-01 | E-GEOD-41466 | biostudies-arrayexpress
Project description:Elucidating the global function of a transcription factor implies the identification of its target genes and genomic binding sites. The role of chromatin in this context is unclear, but the dominant view is that factors bind preferentially to nucleosome-depleted regions, identified as DNaseI-hypersensitive sites (DHS). Here we show by chromatin-IP, MNase and DNaseI assays followed by deep sequencing that the progesterone receptor (PR) requires nucleosomes for optimal binding and function. In breast cancer cells treated with progestins we identified 25,000 PR binding sites (PRbs), the majority encompassing several copies of the hexanucleotide TGTYCY, highly abundant in the genome. We found that functional PRbs accumulate around progesterone-induced genes mainly in enhancers, are enriched in DHS but exhibit high nucleosome occupancy. Progestin stimulation results in remodeling of these nucleosomes with displacement of histones H1 and H2A/H2B dimers. Our results strongly suggest that nucleosomes are crucial for PR binding and hormonal gene regulation. Keywords: time course Whole genome expression microarrays were performed in T47D-MTVL cells stimulated 0, 1 and 6 hr with 10 nM of progestin R5020. 3 biological replicas were performed for T0 and 6 hr treatments and 4 for the one of 1hr.
2012-12-01 | E-GEOD-41502 | biostudies-arrayexpress
Project description:CHD8 is an ATPase of the SNF2 family involved in ATP-dependent nucleosome remodeling. Our data indicate that in the presence of progestin (R5020), a progesterone receptor (PR) agonist, CHD8 is recruited to a number of PR enhancers. To correlate CHD8 binding sites with CHD8-regulated gene expression we performed a transcriptomic analysis of T47D-MTVL cells transfected with a control siRNA or a siRNA specifically targeting CHD8 and stimulated during 6h with progestin or vehicle. CHD8-dependent genes presented lower induction of up-regulated genes and lower repression of down-regulated genes, indicating that CHD8 is required for progesterone-dependent regulation of a subset of genes.
2015-06-01 | GSE62257 | GEO