LILRB3 agonism and antagonism using monocolonal antibodies
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE199380 | GEO | 2025/03/14
REPOSITORIES: GEO
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Project description:LILRB3 agonism and antagonism using monocolonal antibodies
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Project description:Wnt/β-catenin signaling is important in skeletal related-tissue development. We have found that Wnt/β-catenin antagonist XAV could replace traditionally used TGFβ3 as chondrogenic inducer. Here we applied gene expression array to characterize transcriptomic changes between XAV- and TGFβ-induced chondrogenic differentiation in human bone marrow (BM) and induced pluripotent stem cell (iPSC) derived MSCs.
2023-01-04 | GSE211559 | 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.
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. 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 | 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
Project description:Ligands for several transcription factors can act as agonists under some conditions and antagonists under others. The structural and molecular bases of such effects are unknown. Previously, we demonstrated how the folding of intrinsically disordered (ID) protein sequences, in particular, and population shifts, in general, could be used to mediate allosteric coupling between different functional domains, a model that has subsequently been validated in several systems. Here it is shown that population redistribution within allosteric systems can be used as a mechanism to tune protein ensembles such that a given ligand can act as both an agonist and an antagonist. Importantly, this mechanism can be robustly encoded in the ensemble, and does not require that the interactions between the ligand and the protein differ when it is acting either as an agonist or an antagonist. Instead, the effect is due to the relative probabilities of states prior to the addition of the ligand. The ensemble view of allostery that is illuminated by these studies suggests that rather than being seen as switches with fixed responses to allosteric activation, ensembles can evolve to be "functionally pluripotent," with the capacity to up or down regulate activity in response to a stimulus. This result not only helps to explain the prevalence of intrinsic disorder in transcription factors and other cell signaling proteins, it provides important insights about the energetic ground rules governing site-to-site communication in all allosteric systems.
| S-EPMC3306695 | biostudies-literature
Project description:Insulin can trigger metabolic as well as mitogenic effects, the latter being pharmaceutically undesirable. An understanding of the structure/function relationships between insulin receptor (IR) binding and mitogenic/metabolic signalling would greatly facilitate the preclinical development of new insulin analogues. The occurrence of ligand agonism and antagonism is well described for G protein-coupled receptors (GPCRs) and other receptors but in general, with the exception of antibodies, not for receptor tyrosine kinases (RTKs). In the case of the IR, no natural ligand or insulin analogue has been shown to exhibit antagonistic properties, with the exception of a crosslinked insulin dimer (B29-B'29). However, synthetic monomeric or dimeric peptides targeting sites 1 or 2 of the IR were shown to be either agonists or antagonists. We found here that the S961 peptide, previously described to be an IR antagonist, exhibited partial agonistic effects in the 1-10 nM range, showing altogether a bell-shaped dose-response curve. Intriguingly, the agonistic effects of S961 were seen only on mitogenic endpoints ((3)H-thymidine incorporation), and not on metabolic endpoints ((14)C-glucose incorporation in adipocytes and muscle cells). The agonistic effects of S961 were observed in 3 independent cell lines, with complete concordance between mitogenicity ((3)H-thymidine incorporation) and phosphorylation of the IR and Akt. Together with the B29-B'29 crosslinked dimer, S961 is a rare example of a mixed agonist/antagonist for the human IR. A plausible mechanistic explanation based on the bivalent crosslinking model of IR activation is proposed.
| S-EPMC3531387 | biostudies-literature