Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA195464 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Progesterone and estrogen are important drivers of breast cancer proliferation. Herein, we probed estrogen receptor-α (ER) and progesterone receptor (PR) cross-talk in breast cancer models. Stable expression of PR-B in PR-low/ER+ MCF7 cells increased cellular sensitivity to estradiol and insulin-like growth factor 1 (IGF1), as measured in growth assays performed in the absence of exogenous progestin; similar results were obtained in PR-null/ER+ T47D cells stably expressing PR-B. Genome-wide microarray analyses revealed that unliganded PR-B induced robust expression of a subset of estradiol-responsive ER target genes, including cathepsin-D (CTSD). Estradiol-treated MCF7 cells stably expressing PR-B exhibited enhanced ER Ser167 phosphorylation and recruitment of ER, PR and the proline-, glutamate- and leucine-rich protein 1 (PELP1) to an estrogen response element in the CTSD distal promoter; this complex co-immunoprecipitated with IGF1 receptor (IGFR1) in whole-cell lysates. Importantly, ER/PR/PELP1 complexes were also detected in human breast cancer samples. Inhibition of IGF1R or phosphoinositide 3-kinase blocked PR-B-dependent CTSD mRNA upregulation in response to estradiol. Similarly, inhibition of IGF1R or PR significantly reduced ER recruitment to the CTSD promoter. Stable knockdown of endogenous PR or onapristone treatment of multiple unmodified breast cancer cell lines blocked estradiol-mediated CTSD induction, inhibited growth in soft agar and partially restored tamoxifen sensitivity of resistant cells. Further, combination treatment of breast cancer cells with both onapristone and IGF1R tyrosine kinase inhibitor AEW541 was more effective than either agent alone. In summary, unliganded PR-B enhanced proliferative responses to estradiol and IGF1 via scaffolding of ER-α/PELP1/IGF1R-containing complexes. Our data provide a strong rationale for targeting PR in combination with ER and IGF1R in patients with luminal breast cancer.
2015-03-15 | GSE45643 | GEO
Project description:Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a transcriptional coactivator that has previously been shown to collaborate with nuclear receptors. Evidence from other groups suggest that PELP1 may stimulate transcription by displacing the linker histone H1 and/or by recruiting the lysine demethylase KDM1 to demethylate H3K9me2. Also known as modulator of the non-genomic activity of estrogen receptor (MNAR), PELP1 has also been implicated promoting estrogen receptor signaling from the plasma membrane. We recently identified PELP1 a factor that interacts with the macro domain of the histone variant macroH2A1. To determine if PELP1 interacts with macroH2A1 in cells, we performed PELP1 ChIP-chip from MCF-7 cells. The pattern of PELP1 bind across the genome strongly correlates with that previously determined for macroH2A1. This data combined with additional experiments allow us to conclude that macroH2A1 regulates target gene expression in part by recruiting the transcriptional coregulator PELP1. Two PELP1 ChIP-chip biological replicates from MCF-7 human breast cancer cells are included.
2014-04-24 | E-GEOD-22254 | biostudies-arrayexpress
Project description:Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a transcriptional coactivator that has previously been shown to collaborate with nuclear receptors. Evidence from other groups suggest that PELP1 may stimulate transcription by displacing the linker histone H1 and/or by recruiting the lysine demethylase KDM1 to demethylate H3K9me2. Also known as modulator of the non-genomic activity of estrogen receptor (MNAR), PELP1 has also been implicated promoting estrogen receptor signaling from the plasma membrane. We recently identified PELP1 a factor that interacts with the macro domain of the histone variant macroH2A1. To determine if PELP1 interacts with macroH2A1 in cells, we performed PELP1 ChIP-chip from MCF-7 cells. The pattern of PELP1 bind across the genome strongly correlates with that previously determined for macroH2A1. This data combined with additional experiments allow us to conclude that macroH2A1 regulates target gene expression in part by recruiting the transcriptional coregulator PELP1.
2014-04-24 | GSE22254 | GEO
Project description:Examine gene expression for meningioma cases by hormone receptor status and indicate a stronger association with progesterone than with estrogen receptors Experiment Overall Design: The data are surgical specimens from 31 meningioma patients undergoing neuro-surgical resection at Brigham and Womenâs Hospital from 3/15/2004-5/10/2005. Progesterone (PR) and estrogen (ER) hormone receptors were measured via immunohistochemistry and compared with gene expression profiling results.
2008-06-16 | E-GEOD-9438 | biostudies-arrayexpress
Project description:Endometrial cancer (EC) is characterized by high estrogen levels unopposed by progesterone. Treatment with progestins is standard for early EC, but response to progestins is dependent on progesterone receptor (PGR) expression. Here, we show that the expression of PGR in endometrial epithelial cells is dependent on ARID1A, a DNA-binding subunit of the SWI/SNF chromatin remodeling complex that is commonly mutated in EC. In endometrial epithelial cells with estrogen receptor overexpression, we find that ARID1A promotes estrogen signaling and regulates common gene expression programs. Normally, endometrial epithelial cells expressing estrogen receptor respond to estrogen by upregulating the PGR. However, when ARID1A expression is lost, upregulation of PGR expression is significantly reduced. This phenomenon can also occur following loss of the SWI/SNF subunit BRG1, suggesting a role for ARID1A- and BRG1-containing complexes in PGR regulation. We find that PGR is regulated by a bivalent promoter, which harbors both H3K4me3 and H3K27me3 histone tail modifications. H3K27me3 is deposited by EZH2, and inhibition of EZH2 in the context of ARID1A loss results in restoration of estrogen-induced PGR expression. Our results suggest a role for ARID1A deficiency in the loss of PGR in late-stage EC, and a therapeutic utility for EZH2 inhibitors in EC.
2022-03-14 | GSE195503 | GEO
Project description:Epidemiological studies have shown that a full-term pregnancy at early age can decrease the breast cancer risk up to one-half. Pregnancy has been shown to prevent carcinogen-induced mammary tumors in rodents as well. The protective effect of pregnancy can be mimicked by administration of estrogen and progesterone to nulliparous rodents in amounts that are similar to those during pregnancy and alters responsiveness of p53 to DNA damage. Ovariectomized mice were treated with estrogen (E), progesterone (P), both estrogen and progesterone (E + P), or vehicle (V) alone and global expression profiles was analyzed to identify the mechanisms by which estrogen and progesterone combine to sensitize p53 function. Keywords: comparative hormone treatment
2008-07-31 | GSE5483 | GEO
Project description:Small blocks of the midbrain containing the dorsal raphe nucleus was obtained from ovariectomized monkeys treated with placebo, estrogen, progesterone or estrogen plus progesterone for one month. The RNA was extracted and hybridized to the human U95A Affymetrix chip.
2009-05-21 | GSE16171 | GEO
Project description:Epidemiological studies have shown that a full-term pregnancy at early age can decrease the breast cancer risk up to one-half. Pregnancy has been shown to prevent carcinogen-induced mammary tumors in rodents as well. The protective effect of pregnancy can be mimicked by administration of estrogen and progesterone to nulliparous rodents in amounts that are similar to those during pregnancy and alters responsiveness of p53 to DNA damage. Ovariectomized mice were treated with estrogen (E), progesterone (P), both estrogen and progesterone (E + P), or vehicle (V) alone and global expression profiles was analyzed to identify the mechanisms by which estrogen and progesterone combine to sensitize p53 function. Experiment Overall Design: Twenty ovariectomized animals were used for examine transcriptional effects of hormones by microarray. The hormones were administered by daily i.p. injection for 4 days.Treatment groups included: 4 animals receiving 2ug 17-beta-estrogen (E), 4 animals receiving 1mg progesterone (P), 5 animals receiving both estrogen and progesterone (E+P) and 4 animals receiving 100ul sesame oil (V). Epithelial-free fat pads from 3 animals receiving E+P were also analyzed to distinguish responses to E+P in the stroma (E+P CFP). Lymph nodes were removed from mammary glands at the time of collection.
2008-10-18 | E-GEOD-5483 | biostudies-arrayexpress
Project description:SET is a multifunctional histone-binding oncoprotein that regulates transcription by an unclear mechanism. Here, we show that SET enhances estrogen-dependent transcription. SET knockdown abrogates transcription of estrogen-responsive genes and their enhancer RNAs (eRNAs). In response to 17β-estradiol (E2), SET binds to the estrogen receptor α (ERα) and is recruited to estrogen receptor α (ERα)-bound enhancers and promoters at estrogen response elements (EREs). SET functions as a histone H2 chaperone that dynamically associates with H2A.Z via its acidic C-terminal domain and promotes H2A.Z incorporation, ERα, MLL1 and KDM3A loading and modulates histone methylation at EREs. SET depletion diminishes recruitment of condensin complexes to EREs and impairs E2-dependent enhancer-promoter looping. Thus, SET boosts E2-induced gene expression by establishing an active chromatin structure at ERα-bound enhancers and promoters, which is essential for transcriptional activation.
2023-02-02 | GSE218815 | GEO
Project description:SET is a multifunctional histone-binding oncoprotein that regulates transcription by an unclear mechanism. Here, we show that SET enhances estrogen-dependent transcription. SET knockdown abrogates transcription of estrogen-responsive genes and their enhancer RNAs (eRNAs). In response to 17β-estradiol (E2), SET binds to the estrogen receptor α (ERα) and is recruited to estrogen receptor α (ERα)-bound enhancers and promoters at estrogen response elements (EREs). SET functions as a histone H2 chaperone that dynamically associates with H2A.Z via its acidic C-terminal domain and promotes H2A.Z incorporation, ERα, MLL1 and KDM3A loading and modulates histone methylation at EREs. SET depletion diminishes recruitment of condensin complexes to EREs and impairs E2-dependent enhancer-promoter looping. Thus, SET boosts E2-induced gene expression by establishing an active chromatin structure at ERα-bound enhancers and promoters, which is essential for transcriptional activation.
2023-02-01 | GSE200900 | GEO