Estrogen receptor alpha mutations in breast cancer cells cause gene expression changes through constant activity and through secondary effects [RNA-seq]
UID: 10766
- Description
- Summary from the GEO: "While breast cancer patients with tumors that express estrogen receptor α (ER) generally respond well to hormone therapies that block ER’s actions, a significant number relapse. Approximately 30% of these recurrences harbor activating mutations in ER’s ligand binding domain. ER mutations have been shown to confer ligand-independent function to ER; however, much is still unclear regarding the effect of mutant ER beyond its estrogen independence. To investigate mutant ER’s molecular effects, we developed multiple isogenic ER mutant cell lines for the two most common ER ligand binding domain mutations, Y537S and D538G. We found that these mutations induce differential expression of thousands of genes, the majority of which are specific to one or the other mutation and are not observed upon estrogen treatment of wildtype cells. The mutant-specific genes show consistent differential expression across ER mutant lines developed in other laboratories. The observed gene expression changes cannot be explained by constitutive ER activity alone, as wildtype cells with long term estrogen exposure only exhibit some of these transcriptional changes, suggesting that mutant ER causes novel regulatory effects that are not simply due to constant activity. While ER mutations have minor effects on ER genomic binding, with the exception of ligand independence, we observed substantial differences in chromatin accessibility due to ER mutations. Mutant ER is bound to approximately a quarter of mutant-enriched accessible regions that are enriched for other DNA binding factors including FOXA1, CTCF, and OCT1. Our findings indicate that mutant ER causes several consistent effects on gene expression both indirectly and through constant activity."
Overall design from the GEO: "RNA-seq of ESR1 mutant and wildtype MCF-7 and T-47D breast cancer cell lines."
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Access via GEO
Plain Text files of expression profiling by high throughput sequencing
Accession #: GSE148276Access via SRARNA sequencing of 44 samples.
Accession #: SRP255664Access via BioProjectAdditional information about the overall inititative.
Accession #: PRJNA623671 - Access Restrictions
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Free to All
- Access Instructions
- The NCBI Gene Expression Omnibus, SRA and BioProject databases provide open access to these files. SRA and/or tar files can be downloaded directly from the site or viewed in the NCBI SRA Run Selector (link at bottom of page).
- Associated Publications
- Data Type
- Equipment Used
- Software Used
- Dataset Format(s)
- Plain Text, SRA
- Data Tool(s)
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RNA Seq
- Dataset Size
- 1.53 MB (TXT), 34.7 Gb (SRA)
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