Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA235334 | ENA |
REPOSITORIES: ENA
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Project description:Estrogen- and Myc-regulated genes in MCF-7 breast cancer cells
| PRJNA105991 | ENA
Project description:A c-Src inhibitor blocks estrogen (E2)-induced stress and converts E2 responses from inducing apoptosis to growth stimulation in E2-deprived breast cancer cells. A reprogrammed cell line, MCF-7:PF, results with features of functional estrogen receptor (ER) and over-expression of insulin-like growth factor-1 receptor beta (IGF-1Rβ). We addressed the question of whether the selective ER modulator 4-hydroxytamoxifen (4-OHT) could target ER to prevent E2-stimulated growth in MCF-7:PF cells. Selected expression of mRNA was measured through real-time RT-PCR. Global gene expression was analyzed by microarray and RNA-seq analysis. Unexpectedly, both 4-OHT and E2 stimulated cell growth in a concentration-dependent manner. Global gene expression analysis showed a remarkable overlap in genes regulated in the same direction by E2 and 4-OHT. Pathway enrichment analysis of the 280 genes commonly deregulated by 4-OHT and E2 revealed functions mainly related to membrane, cytoplasm, and metabolic processes. Further analysis of 98 up-regulated genes by both 4-OHT and E2 uncovered a significant enrichment in genes associated with membrane remodeling, cytoskeleton reorganization, cytoplasmic adapter proteins, cytoplasm organelles proteins, and related processes. 4-OHT was more potent than E2 to up-regulate some membrane remodeling molecules, such as EHD2, FHL2, HOMER3 and RHOF. In contrast, 4-OHT acted as an antagonist to inhibit expression of the majority of enriched membrane-associated genes in wild-type MCF-7 cells. Long-term selection pressure has changed the cell population responses to 4-OHT. Membrane-associated signaling is critical for 4-OHT-stimulated cell growth in MCF-7:PF cells. This study provides a rationale for the further investigation of targeted therapy for tamoxifen resistant patients. Wild-type MCF-7 cells were treated with vehicle control (0.1% ethanol), E2 (10-9 mol/L) and 4-OHT (10-6 mol/L) respectively for 24 hours.
2014-07-18 | E-GEOD-59536 | biostudies-arrayexpress
Project description:A c-Src inhibitor blocks estrogen (E2)-induced stress and converts E2 responses from inducing apoptosis to growth stimulation in E2-deprived breast cancer cells. A reprogrammed cell line, MCF-7:PF, results with features of functional estrogen receptor (ER) and over-expression of insulin-like growth factor-1 receptor beta (IGF-1Rβ). We addressed the question of whether the selective ER modulator 4-hydroxytamoxifen (4-OHT) could target ER to prevent E2-stimulated growth in MCF-7:PF cells. Selected expression of mRNA was measured through real-time RT-PCR. Global gene expression was analyzed by microarray and RNA-seq analysis. Unexpectedly, both 4-OHT and E2 stimulated cell growth in a concentration-dependent manner. Global gene expression analysis showed a remarkable overlap in genes regulated in the same direction by E2 and 4-OHT. Pathway enrichment analysis of the 280 genes commonly deregulated by 4-OHT and E2 revealed functions mainly related to membrane, cytoplasm, and metabolic processes. Further analysis of 98 up-regulated genes by both 4-OHT and E2 uncovered a significant enrichment in genes associated with membrane remodeling, cytoskeleton reorganization, cytoplasmic adapter proteins, cytoplasm organelles proteins, and related processes. 4-OHT was more potent than E2 to up-regulate some membrane remodeling molecules, such as EHD2, FHL2, HOMER3 and RHOF. In contrast, 4-OHT acted as an antagonist to inhibit expression of the majority of enriched membrane-associated genes in wild-type MCF-7 cells. Long-term selection pressure has changed the cell population responses to 4-OHT. Membrane-associated signaling is critical for 4-OHT-stimulated cell growth in MCF-7:PF cells. This study provides a rationale for the further investigation of targeted therapy for tamoxifen resistant patients.
2014-07-18 | GSE59536 | GEO
Project description:MCF-7:PF is a a new in vitro model of antihormone resistant breast cancer that exhibits the characteristics of acquired tamoxifen resistance in vivo. It is well known that estrogen (E2) induces apoptosis in long-term estrogen-deprived breast cancer cells, MCF-7:5C (PubMed References PMID:15862958, PMID:16333030). MCF-7:PF was derived from MCF-7:5C through inhibition of c-Src, which blocks E2-induced apoptosis, coverts E2 responses from apoptosis to proliferation. MCF-7:PF cell growth is stimulated by E2 and SERMS in an ERα-dependent manner. Abstract: A c-Src inhibitor blocks estrogen (E2)-induced stress and converts E2 responses from inducing apoptosis to stimulating growth in E2-deprived breast cancer cells. A resulting cell line, MCF-7:PF, is reprogrammed with features of functional estrogen receptor (ER) and over-expression of insulin-like growth factor-1 receptor beta (IGF-1Rβ). We addressed the question of whether the antiestrogenic selective ER modulator 4-hydroxytamoxifen (4-OHT) could target ER to prevent E2-stimulated growth in MCF-7:PF cells. Unexpectedly, 4-OHT stimulated cell growth in an ER-dependent manner. However, unlike E2, 4-OHT suppressed classic ER-target genes as does the pure antiestrogen ICI 182,780, even during growth stimulation. Chromatin-immunoprecipitation (ChIP) assay indicated that 4-OHT did not recruit ER or nuclear receptor coactivator 3 (SRC3) to the promoter of ER-target gene, pS2. Paradoxically, 4-OHT reduced total IGF-1Rβ but increased phosphorylation of IGF-1Rβ, which was responsible for the activation of the phosphatidylinositol-3 kinases (PI3K)/Akt signaling pathway. Mechanistic studies revealed that 4-OHT rapidly activated the non-genomic pathway through ER, but other membrane-associated proteins such as IGF-1Rβ and c-Src participated. Furthermore, 4-OHT was more potent than E2 to up-regulate membrane remodeling molecules and activated focal adhesion molecules to promote cell growth. Therefore, disruption of membrane-associated signaling completely abolished 4-OHT-stimulated cell growth, but not E2-stimulated cell growth. Despite continued suppression of classic ER-target genes, 4-OHT activated the complex network of cytoskeleton remodeling and extracellular matrix-related signaling which facilitated 4-OHT-stimulated cell growth. This study is the first to recapitulate a cellular model in vitro of acquired tamoxifen (TAM) resistance developed in athymic mice in vivo.
2014-07-14 | GSE54171 | GEO
Project description:Downstream genes regulated by TSHZ2 in MCF-7 cells
| PRJNA270804 | ENA
Project description:Estrogen receptor-mediated proliferation of breast cancer cells is facilitated through expression of multiple primary target genes, products of which induce the secondary response to stimulation. To differentiate between the primary and secondary target genes of estrogen receptor signaling, we measured dynamics of protein expression induced by estradiol in MCF-7 breast cancer cells. Measurement of the global proteomic effects of estradiol by SILAC resulted in identification of 104 estradiol-regulated proteins, with only 41 corresponding genes having estrogen response elements (EREs). Selected reaction monitoring assays were used to validate 32 proteins and measure the dynamics of their expression within 72 hours upon estradiol stimulation and in the presence of 4-hydroxytamoxifen, thus confirming estrogen receptor-mediated signaling. Dynamics of protein expression revealed immediate early response proteins including TFF1 and CDK1 and delayed response proteins including CDK2 and NAB2. Presence or absence of EREs in the corresponding genes indicated early or delayed expression of proteins identified by SILAC. Finally, we measured accurate dynamics of estradiol-induced protein expression in the sub-network of primary and secondary targets of estrogen receptor. Interestingly, since NAB2 protein is also a repressor of EGR3-induced transcription, siRNA-mediated silencing of NAB2 resulted in the over-expression of some EGR3-induced proteins, such as ITGA2. To conclude, quantitative proteomics revealed secondary targets of estrogen receptor signaling potentially overlooked by genome-wide profiling of EREs and provided dynamics of protein expression in the network of transcription factors with a negative feedback loop.
2016-04-14 | PXD002797 | Pride
Project description:MCF-7:5C and MCF-7:2A are two in vitro models of Estrogen Receptor alpha positive (ER+) estrogen deprivation-resistant breast cancer. Both cell lines grow robustly in the absence of estrogen [PMID:1301400, PMID:7780972]. MCF-7:PF is an in vitro model of antihormone resistant breast cancer that exhibits the characteristics of acquired tamoxifen resistance [PMID:24183378] The goal of this study was to compare basal levels of gene expression during exponential phase of growth in MCF-7-derived models of endocrine resistance, relative to their isogenic parental cells
2014-11-30 | GSE60079 | GEO
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes
2014-08-06 | GSE58734 | GEO