GSE148276 Estrogen receptor alpha mutations in breast cancer cells cause gene expression changes through constant activity and through secondary effects RNA-seq

Contributors : Spencer Arnesen ; Jason GertzSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensWhile 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 diff erential 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 obs erved 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 lig...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research

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