Similar Datasets
Project description:Purpose: Transcriptome analysis of ESR1 mutant cells was performed via sequencing total RNA in T47D and MCF7 cell lines containing Y537S and D538G mutations.
2017-06-03 | GSE89888 | GEO
Project description:We investigated the therapeutic potential of BET inhibition to target ESR1 mutation-induced “transcriptional addiction” in ER-positive breast cancer. Our studies show that ESR1 mutant (Y537S and D538G) cells activate unique transcriptional programs that are targeted by OTX015, a BET inhibitor
2022-06-18 | GSE206185 | GEO
Project description:RNAseq of cell lines with knocked in ESR1 mutations
| PRJNA445373 | ENA
Project description:This study is designed to comprehensively characterize the FOXA1 cistromes of Y537S and D538G mutated ER versus WT ER in breast cancer cells.
2022-04-01 | GSE165280 | GEO
Project description:Estrogen receptor (ER) is the major driver of a large proportion of breast cancers, and many therapies have been designed to target it. These include anti-estrogens, which target ER directly, and aromatase inhibitors, which instead prevent the biosynthesis of estrogen in post-menopausal women. These therapies have been largely successful, but unfortunately many patients eventually succumb to resistance. A hotspot of mutations in exon 8 of ESR1, which cause the ER to be constitutively active, have been discovered in advanced breast cancer patients, and are one cause of resistance to aromatase inhibitors as well as a reduced response to anti-estrogen therapies. Since most studies in to these mutations have so far focused on the mostly commonly seen mutations, Y537S and D538G, it is important to extend our understanding to other frequently found mutations to determine whether there are intrinsic differences between them. For this purpose, CRISPR-Cas9 was used in order to model the following mutations found in exon 8 of ESR1 in breast cancer patients, L536R, Y537C, Y537S, Y537N and D538G, in MCF7 cells, with between two to four clones of each mutation generated. Growth in the absence of estrogen and in the presence of various SERDs was tested to investigate differences in sensitivity between mutations. RNA-seq was carried out in the ESR1 mutant MCF7 lines under full medium conditions to look for gene expression changes compared to WT, shared between all mutations, or the possibility of differences between specific mutations, which were not due to the fact that the ESR1 mutant lines can grow in the absence of estrogen. The results of which should provide great insight into potential alternative genes or pathways, which could be targeted in patients harbouring these mutations.
2022-08-09 | GSE147745 | GEO
Project description:Three quarters of all breast cancer cases express the estrogen receptor (ER, ESR1 gene), which promotes tumor growth and constitutes a direct target for endocrine therapies. ESR1 mutations have been implicated in therapy resistance in metastatic breast cancers, in particular to aromatase inhibitors. ESR1 mutations promote constitutive ER activity and affect other signaling pathways, allowing cancer cells to proliferate by employing mechanisms within and outwith direct regulation by the ER. Although subjected to extensive genetic and transcriptomic analyses, understanding of protein alterations remains poorly investigated. Towards this, we employed an integrated mass spectrometry (MS) based proteomic approach to profile the protein and phosphoprotein differences in breast cancer cell lines expressing the frequent Y537N and Y537S ER mutations. Global proteome analysis revealed enrichment of mitotic and immune signaling pathways in ER mutant cells, while phosphoprotein analysis evidenced enriched activity of proliferation associated kinases, in particular CDKs and MTOR. Integration of protein expression and phosphorylation data revealed pathway-dependent discrepancies (motility vs proliferation) that were observed at varying degrees across mutant and wt ER cells. Additionally, protein expression and phosphorylation patterns, while under different regulation, still recapitulated the estrogen-independent phenotype of ER mutant cells.
2024-03-26 | PXD032369 | Pride
Project description:Three quarters of all breast cancer cases express the estrogen receptor (ER, ESR1 gene), which promotes tumor growth and constitutes a direct target for endocrine therapies. ESR1 mutations have been implicated in therapy resistance in metastatic breast cancers, in particular to aromatase inhibitors. ESR1 mutations promote constitutive ER activity and affect other signaling pathways, allowing cancer cells to proliferate by employing mechanisms within and outwith direct regulation by the ER. Although subjected to extensive genetic and transcriptomic analyses, understanding of protein alterations remains poorly investigated. Towards this, we employed an integrated mass spectrometry (MS) based proteomic approach to profile the protein and phosphoprotein differences in breast cancer cell lines expressing the frequent Y537N and Y537S ER mutations. Global proteome analysis revealed enrichment of mitotic and immune signaling pathways in ER mutant cells, while phosphoprotein analysis evidenced enriched activity of proliferation associated kinases, in particular CDKs and MTOR. Integration of protein expression and phosphorylation data revealed pathway-dependent discrepancies (motility vs proliferation) that were observed at varying degrees across mutant and wt ER cells. Additionally, protein expression and phosphorylation patterns, while under different regulation, still recapitulated the estrogen-independent phenotype of ER mutant cells.
2024-03-26 | PXD032404 | Pride
Project description:Biotinylated 4xERE-containing DNA immobilized on streptavidin beads used to pulldown proteins recruited by unliganded WT ER-alpha versus Y537S, D538G, or ESR1-YAP1 fusion proteins from HeLa S3 human cell nuclear extracts.
2017-02-08 | MSV000080536 | MassIVE
Project description:Analysis of MCF7 cells transfected with ER mutants (S463P, Y537S and D538G) in phenol-red free, charcoal stripped FBS media and regular DMEM/F12 media. Results provide insight on the gene expression profiles induced by the various ER mutants. Total RNA extracted from transfected cells 48 hours after transfection 36 samples were analyzed, triplicates for each constructs (GFP vector control, WT, S463P, Y537S, D538G and S463P/D538G) for each type of media
2013-10-25 | E-GEOD-51448 | biostudies-arrayexpress
Project description:Three quarters of all breast cancer cases express the estrogen receptor (ER, ESR1 gene), which promotes tumor growth and constitutes a direct target for endocrine therapies. ESR1 mutations have been implicated in therapy resistance in metastatic breast cancers, in particular to aromatase inhibitors. ESR1 mutations promote constitutive ER activity and affect other signaling pathways, allowing cancer cells to proliferate by employing mechanisms within and outwith direct regulation by the ER. Although subjected to extensive genetic and transcriptomic analyses, understanding of protein alterations remains poorly investigated. Towards this, we employed an integrated mass spectrometry (MS) based proteomic approach to profile the protein and phosphoprotein differences in breast cancer cell lines expressing the frequent Y537N and Y537S ER mutations. Global proteome analysis revealed enrichment of mitotic and immune signaling pathways in ER mutant cells, while phosphoprotein analysis evidenced enriched activity of proliferation associated kinases, in particular CDKs and MTOR. Integration of protein expression and phosphorylation data revealed pathway-dependent discrepancies (motility vs proliferation) that were observed at varying degrees across mutant and wt ER cells. Additionally, protein expression and phosphorylation patterns, while under different regulation, still recapitulated the estrogen-independent phenotype of ER mutant cells.
2024-03-26 | PXD032285 | Pride