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| Status |
Public on Sep 01, 2013 |
| Title |
Co-regulated gene expression by estrogen receptor-α and liver receptor homolog-1 is a feature of the estrogen response in breast cancer cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Estrogen receptor α (ERα) is a nuclear receptor that is the driving transcription factor expressed in the majority of breast cancers. Recent studies have demonstrated that the liver receptor homolog-1 (LRH-1), another nuclear receptor, is ERα-regulated in breast cancer cells. Further, LRH-1 stimulates proliferation and promotes motility and invasion of breast cancer cells. To determine the mechanisms of LRH-1 action in breast cancer cells, we carried out gene expression microarray analysis following siRNA-mediated LRH-1 knockdown. Interestingly, gene ontology (GO) category enrichment analysis of the genes differentially regulated in the presence or absence of LRH-1 identified estrogen responsive genes as the most highly enriched GO categories. To further define LRH-1 target genes, we performed chromatin immunoprecipitation coupled to massively parallel sequencing (ChIP-seq) to identify genomic targets of LRH-1. Remarkably, ChIP-seq showed LRH-1 binding at many ERα binding sites. Analysis of select binding sites confirmed regulation of ERα-regulated genes by LRH-1 through binding to estrogen response elements, as exemplified by the TFF1/pS2 gene. Finally, LRH-1 over-expression stimulated ERα recruitment, whilst LRH-1 knockdown reduced ERα recruitment to ERα binding sites. Taken together, our findings establish a key role for LRH-1 in the regulation of ERα target genes in breast cancer cells and identify a mechanism in which co-operative binding of LRH-1 and ERα at estrogen response elements controls the expression of estrogen-responsive genes.
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| Overall design |
MCF-7 cells were transfected with LRH-1 siRNA #2, #3, or with a non-targeting siRNA (siControl) for 72 hours. Following assessment of RNA integrity, four biological replicates for each siRNA treatment were used for microarray analysis.
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| Contributor(s) |
Lai CF, Thiruchelvam P, Ottaviani S, Ali S |
| Citation(s) |
24049078 |
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| Submission date |
Jun 10, 2013 |
| Last update date |
Aug 16, 2018 |
| Contact name |
Simak Ali |
| E-mail(s) |
simak.ali@imperial.ac.uk
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| Organization name |
Imperial College London
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| Department |
Department of Surgery & Cancer
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| Street address |
Du Cane Road
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| City |
London |
| ZIP/Postal code |
W12 0NN |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL6947 |
Illumina HumanHT-12 V3.0 expression beadchip |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA207825 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE47803_RAW.tar |
6.2 Mb |
(http)(custom) |
TAR |
| GSE47803_non-normalized.txt.gz |
2.5 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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