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E-GEOD-30574 - Cellular reprogramming by the conjoint action of ERalpha, FOXA1, and GATA3 to a ligand inducible growth state

Status
Released on 4 September 2011, last updated on 14 September 2011
Organism
Homo sapiens
Samples (36)
Array (1)
Protocols (6)
Description
Despite the role of the estrogen receptor alpha (ERalpha) pathway as a key growth driver for breast cells, the phenotypic consequence of exogenous introduction of ERalpha into ERalpha-negative cells paradoxically has been growth inhibition. We map the binding profiles of ERalpha and its interacting transcription factors (TFs), FOXA1 and GATA3 in MCF-7 breast carcinoma cells. We observe that these three TFs form a functional enhanceosome and cooperatively modulate the transcriptional networks previously ascribed to ERalpha alone. We demonstrate that these enhanceosome occupied sites are associated with optimal enhancer characteristics with highest p300 coactivator recruitment, RNA Pol II occupancy, and chromatin opening. The enhancesome binding sites appear to regulate the genes driving core ERalpha function. Most importantly, we show that the transfection of all three TFs was necessary to reprogramme the ERalpha-negative MDA-MB-231 and BT-459 cells to restore the estrogen responsive growth and to transcriptionally resemble the estrogen treated ERalpha-positive MCF-7 cells. Cumulatively, these results suggest that all the enhanceosome components comprising ERalpha, FOXA1 and GATA3 are necessary for the full repertoire of cancer associated effects of the ERalpha. Illumina HumanRef-8 v3 Expression BeadChip was used to measure the gene expression levels from ERalpha negative breast cancer cell MDA-MB-231 with different transfections: with vector control, with ERalpha only, or with ERalpha+FOXA1+GATA3 combined.
Experiment type
transcription profiling by array 
Contacts
Guoliang Li <ligl@gis.a-star.edu.sg>, Edison T Liu, Say L Kong
Citation
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-30574.idf.txt
Sample and data relationshipE-GEOD-30574.sdrf.txt
Processed data (1)E-GEOD-30574.processed.1.zip
Array designA-MEXP-1172.adf.txt
Links