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Series GSE25315 Query DataSets for GSE25315
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
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.
 
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.
 
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 roslin.russell@cruk.cam.ac.uk
Phone 01223 769770
Organization name Cambridge Research Institute, Cancer Research UK
Street address Robinson Way
City Cambridge
ZIP/Postal code CB2 0RE
Country United Kingdom
 
Platforms (1)
GPL10558 Illumina HumanHT-12 V4.0 expression beadchip
Samples (12)
GSM622773 si Control and vehicle replicate 1
GSM622774 si FoxA1 and vehicle replicate 1
GSM622775 si Control and estrogen replicate 1
This SubSeries is part of SuperSeries:
GSE25316 FoxA1 is a critical determinant of Estrogen Receptor function and endocrine response
Relations
BioProject PRJNA142547

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE25315_RAW.tar 26.2 Mb (http)(custom) TAR
GSE25315_non-normalized.txt.gz 2.1 Mb (ftp)(http) TXT
GSE25315_normalized.txt.gz 3.1 Mb (ftp)(http) TXT
Raw data is available on Series record
Processed data is available on Series record
Processed data included within Sample table

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