Measuring the transcriptomic response to targeting kinases correlated with estrogen receptor activity in Breast Cancer
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PROVIDER: PRJNA549696 | ENA |
REPOSITORIES: ENA
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Project description:We undertook a phosophotranscriptomic network analysis of published patient tumour RNA-seq and phosphoproteomic data to identify kinases that correltated with Estrogen Receptor activity in Breast Cancer. The most sucessful canidates were selected for targeting by siRNA and the effects monitored by RNA-seq. The code for generation of the expression matrix is available from https://github.com/andrewholding/SimonaVIPER
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Project description:We found by RNA seq analysis that the expression of the cyclin D1 gene, the classic target of estrogen-stimulated transcription through an AP1 response element, negatively correlated with that of ERβ/ESR2 as measured using Spearman correlation coefficient (rho = -0.45, p = 0.005). ERβ/ESR2 expression was also negatively correlated with that of ERα/ESR1 (rho = -0.35, p = 0.033). However, ERβ/ESR2 mRNA expression positively correlated with that of IGFBP4 (rho = 0.58, p < 0.001) and CXCL12 (rho = 0.54, p < 0.001). The univariate Cox proportional hazards estimate for overall survival by ESR2 expression was 0.54 (95% CI 0.06, 5.22), suggesting a positive trend that did not reach statistical significance in this numerically limited cohort .
2022-05-18 | GSE198545 | GEO
Project description:Estrogen action is mediated by various genes including estrogen-responsive genes (ERGs). ERGs have been used as markers for gene expression and as reporter-genes, while gene expression profiling using a set of ERGs has been used as statistically reliable transcriptomic assays, such as DNA microarray assays and RNA-seq. However, the quality of ERGs has not been extensively examined. Here, we found a set of 300 ERGs newly identified by six sets of RNA-seq data obtained from estrogen-treated and control human breast cancer MCF-7 cells. The ERGs exhibited statistical stability as judged by the coefficient of variation (CV) analysis, and their usefulness as markers for estrogenic activity by examining the stability of data in the study of correlation analysis, and functional association with estrogen action through database searches. A set of the top 30 genes based on CV ranking were further evaluated quantitatively by RT-PCR and qualitatively by a functional analysis using GO and KEGG databases and by a mechanistic analysis to classify ERα/β-dependent or ER-independent types of transcriptional regulation. The 30 ERGs were characterized by (1) the enzymes, such as metabolic enzymes, proteases and protein kinases, (2) the genes with specific cell functions, such as cell-signaling mediators, tumor-suppressors and the roles in breast cancer, (3) the association with transcriptional regulation, and/or (4) estrogen-responsiveness. Therefore, the ERGs identified here could represent various cell functions and cell signaling pathways including estrogen signaling, and thus, would be useful to evaluate estrogenic activity.
2022-08-26 | GSE205784 | GEO
Project description:Bioenergetic Activity is Correlated with Apomeiosis in Sorghum Ovules
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Project description:Background: Clinical trial and epidemiological data support that the cardiovascular effects of estrogen are complex, including a mixture of both potentially beneficial and harmful effects. In animal models, estrogen protects females from vascular injury and inhibits atherosclerosis. These effects are mediated by estrogen receptors (ERs), which when bound to estrogen can bind to DNA to directly regulate transcription. ERs can also activate several cellular kinases by inducing a M-bM-^@M-^\rapidM-bM-^@M-^] non-nuclear signaling cascade. However, the biologic significance of this rapid signaling pathway has been unclear. Methods and Results: Here, we develop a novel transgenic mouse in which rapid signaling is blocked by over-expression of a peptide that prevents ERs from interacting with the scaffold protein, striatin (the Disrupting Peptide Mouse, DPM). Microarray analysis of ex vivo-treated mouse aortas demonstrates that rapid ER signaling plays an important role in E2-mediated gene regulatory responses. Disruption of ER-striatin interactions also eliminates the ability of E2 to stimulate cultured endothelial cell migration and to inhibit cultured vascular smooth muscle cell growth. The importance of these findings is underscored by in vivo experiments demonstrating loss of estrogen-mediated protection against vascular injury in the DPM mouse following carotid artery wire injury. Conclusions: Taken together, these results support that rapid, non-nuclear ER signaling contributes to the transcriptional regulatory functions of ER, and is essential for many of the vasoprotective effects of estrogen. These findings also identify the rapid ER signaling pathway as a potential target for the development of novel therapeutic agents. Transgenic disrupting peptide mice (DPM) express the Estrogen Receptor (ER) alpha amino acids 176-253 peptide under CMV promoter control. This peptide blocks interactions between ER and striatin, which inhibits rapid non-genomic signaling by ER to cellular kinases. Female WT and DPM mice (4 mice per sample) were overiectomized, and 1 week later aortas were harvested and treated + 10 nM beta-estradiol (E2) or + EtOH vehicle (Veh) for 4 hrs ex vivo. Total RNA was collected, reverse transcribed to cDNA and used to probe Affymetrix mouse 430.A 2.0 arrays.
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Project description:The Estrogen Receptor alpha (ERα) controls key cellular functions in hormone responsive breast cancer by assembling in large functional multiprotein complexes. ERα ligands are classified as agonists and antagonist, according to the response they elicit, thus the molecular characterization of the of ERα nuclear iteractome composition following estrogen and antiestrogen stimulation whose is needed to understand their effects on estrogen target tissues, in particular breast cancer. To this aim interaction proteomics coupled to mass spectrometry (MS) was applied to map the ERα nuclear interacting partners in MCF7 breast cancer cell nuclei following estrogen and antiestrogen stimuli.
2020-09-02 | PXD018709 | Pride
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