A5038042793- Estrogen and related hormone effects
- Endometrial and Cervical Cancer Treatments
- 14-3-3 protein interactions
- Computational Drug Discovery Methods
- Nutrition, Genetics, and Disease
- Cancer Cells and Metastasis
- Glutathione Transferases and Polymorphisms
- Ovarian cancer diagnosis and treatment
- Genomics and Chromatin Dynamics
- Protein Degradation and Inhibitors
- Cytokine Signaling Pathways and Interactions
- Cancer Immunotherapy and Biomarkers
- Advanced Breast Cancer Therapies
- Synthesis and Biological Evaluation
- Cancer therapeutics and mechanisms
- Circular RNAs in diseases
- Science, Research, and Medicine
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- MicroRNA in disease regulation
- Gene expression and cancer classification
- RNA and protein synthesis mechanisms
- Turfgrass Adaptation and Management
- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
Huntsman Cancer Institute
2018-2023
University of Utah
2018-2023
Brigham Young University
2017
Constitutively active estrogen receptor α (ER/ESR1) mutations have been identified in approximately one-third of ER+ metastatic breast cancers. Although these are known as mediators endocrine resistance, their potential role promoting disease has not yet mechanistically addressed. In this study, we show the presence ESR1 exclusively distant but local recurrences five independent cancer cohorts. concordance with transcriptomic profiling ESR1-mutant tumors, genome-edited Y537S and D538G-mutant...
Estrogen receptor 1 (
Activating estrogen receptor alpha (ER; also known as ESR1) mutations are present in primary endometrial and metastatic breast cancers, promoting estrogen-independent activation of the receptor. Functional characterizations cancer have established unique molecular phenotypic consequences receptor, yet impact ER has not been fully explored. In this study, we used CRISPR-Cas9 to model clinically prevalent ER-Y537S mutation compared results with ER-D538G discover allele-specific differences...
PREMISE OF THE STUDY: Invasive species are often initially restricted to a narrow range and may then expand through any of multiple mechanisms including phenotypic plasticity, in situ evolution, or selection on traits preadapted for new habitats. Our study used population genetics explore possible processes by which the highly selfing invasive annual grass Bromus tectorum has expanded into montane environments. METHODS: We 69 single nucleotide polymorphic (SNP) markers genotype ca. 20...
Abstract Estrogen receptor α (ER) mutations occur in up to 30% of metastatic ER-positive breast cancers. Recent data has shown that ER impact the expression thousands genes not typically regulated by wildtype ER. While majority these altered can be explained constant activity mutant or genomic changes such as binding and chromatin accessibility, much 33% remain unexplained, indicating potential for post-transcriptional effects. Here, we explored role microRNAs ER-driven gene regulation...
Abstract Estrogen receptor 1 ( ESR1 ) mutations have been identified in hormone therapy resistant breast cancer and primary endometrial cancer. Analyses suggests that mutant exhibits estrogen independent activity. In cancer, are associated with worse outcomes less obesity, however experimental investigation of these has not performed. Using a unique CRISPR/Cas9 strategy, we introduced the D538G mutation, common mutation alters ligand binding domain ESR1, while epitope tagging endogenous...
<p>ER mutants do not affect proliferation, but down-regulate proteins associated with movement and impact migration</p>
<p>Supplementary Materials and Methods</p>
<p>Differentially expressed genes from in vitro RNA-seq experiments</p>
<p>Identification of novel therapeutic targets in ER active and mutant endometrial cancer</p>
<p>Comparison of mutant ER regulated genes and by sustained estrogen signaling</p>
<p>Mutant ESR1 generation: gBlock used for template amplification</p>
<p>In vivo exploration of novel therapeutic targets in ER active and mutant endometrial cancer</p>
<p>ER-Y537S and ER-D538G mutants drive proliferative gene expression signatures in vivo</p>
<p>ER binding is altered by the Y537S and D538G mutations</p>
<p>Validation and gene expression analysis of ER mutant models</p>
<p>Enrichment values for ER associating proteins in endometrial and breast cancer cell lines</p>
<p>Differentially expressed genes from in vivo RNA-seq experiments</p>
<p>Overlap between prolonged E2 treatment and differentially expressed genes in vitro</p>
<p>In vivo exploration of novel therapeutic targets in ER active and mutant endometrial cancer</p>
<p>Supplementary Materials and Methods</p>
<p>Enrichment values for ER associating proteins in endometrial and breast cancer cell lines</p>
<p>Identification of novel therapeutic targets in ER active and mutant endometrial cancer</p>