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| Status |
Public on Nov 17, 2010 |
| Title |
FoxA1 is a critical determinant of Estrogen Receptor function and endocrine response (part II) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Estrogen Receptor-a (ER) is the key feature in the majority of breast cancers and ER binding to the genome correlates with the Forkhead protein FOXA1 (HNF3a), but mechanistic insight is lacking. We now show that FOXA1 is the defining factor that governs differential ER-chromatin interactions. We show that almost all ER-chromatin interactions and gene expression changes are dependent on the presence of FOXA1 and that FOXA1 dictates genome-wide chromatin accessibility. Furthermore, we show that CTCF is an upstream negative regulator of FOXA1-chromatin interactions. In ER responsive breast cancer cells, the dependency on FOXA1 for tamoxifen-ER activity is absolute and in tamoxifen resistant cells, ER binding occurs independently of ligand, but in a FOXA1 dependent manner. Importantly, expression of FOXA1 in non-breast cancer cells is sufficient to alter ER binding and response to endocrine treatment. As such, FOXA1 is the primary determinant that regulates estrogen-ER activity and endocrine response in breast cancer cells and is sufficient to program ER functionality in non-breast cancer contexts.
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| Overall design |
FoxA1 silenced breast cancer MCF-7 cell lines or control siRNA in the presence of Estrogen or a vehicle. MCF-7 cells were hormone-depleted for 3 d and treated with 100 nM estrogen for 6 h. There were three biological replicates for each of the four different groups.
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| Contributor(s) |
Rodriguez AH, Carroll JS, Russell R |
| Citation(s) |
21151129 |
| Submission date |
Nov 12, 2010 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Roslin Russell |
| E-mail(s) |
roslin.russell@cruk.cam.ac.uk
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| Phone |
01223 769770
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| Organization name |
Cambridge Research Institute, Cancer Research UK
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| Street address |
Robinson Way
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| City |
Cambridge |
| ZIP/Postal code |
CB2 0RE |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE25316 |
FoxA1 is a critical determinant of Estrogen Receptor function and endocrine response |
|
| Relations |
| BioProject |
PRJNA142547 |
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