Taken together, these results define a paradigm for estrogen action in breast cancer cells and suggest that regulation of gene expression by nuclear receptors can be compartmentalized into unique transcriptional domains by means of licensing of their activity to cofactors such as FOXA1.
RNA and protein analysis as well as immunohistochemistry showed that expression of FOXA1 correlated with the expression of the estrogen receptor in a panel of breast cancer cell lines and tissues.
The transcription factor network composed of the oestrogen (estrogen) receptor alpha (ERalpha), FOXA1 and GATA3 may control the gene expression pattern in luminal subtype A breast cancers.
Analysis of publicly available databases revealed ERalpha-positive/T-bet-positive breast cancers expressing lower levels of FOXA1 (P = 0.0137) and GATA-3 (P = 0.0063) compared with ERalpha-positive/T-bet-negative breast cancers.
In this resource paper, we present the genome-wide localization analysis of SRC-3 chromatin affinity sites in MCF-7 human breast cancer chromatin and compare the cis binding sites to global cartographies for ER and FoxA1.
These data reveal that FOXA1 is necessary for hormonal responsiveness in the developing mammary gland and ERalpha-positive breast cancers, at least in part, through its control of ERalpha expression.
Estrogen receptor (ER) is regarded as a major causal factor in breast cancer and FoxA1, a winged-helix transcription factor belonging to the forkhead family, has been found to function as a pioneer factor in the recruitment of ER to several cis-regulatory elements in the genome.
Estrogen receptor-α (ER) is the key feature of most breast cancers and binding of ER to the genome correlates with expression of the Forkhead protein FOXA1 (also called HNF3α).
Chromatin immunoprecipitation assays in T-47D human breast cancer cells revealed a TCDD-dependent recruitment of AHR, nuclear co-activator 3 (NCoA3) and the transcription factor forkhead box A1 (FOXA1), a key regulator of breast cancer cell signaling, to CCNG2 resulting in increases in CCNG2 mRNA and protein levels.
Our results show that breast cancer risk-associated SNPs are enriched in the cistromes of FOXA1 and ESR1 and the epigenome of histone H3 lysine 4 monomethylation (H3K4me1) in a cancer- and cell type-specific manner.
Our results show that breast cancer risk-associated SNPs are enriched in the cistromes of FOXA1 and ESR1 and the epigenome of histone H3 lysine 4 monomethylation (H3K4me1) in a cancer- and cell type-specific manner.
A new study shows that SNPs associated with breast cancer risk are located in enhancer regions and alter binding affinity for the pioneer factor FOXA1.
A conserved PR binding element was identified in PR binding regions from both cell lines, but there were distinct patterns of enrichment of known cofactor binding motifs, with FOXA1 sites over-represented in breast cancer cell binding regions and NF1 and AP-1 motifs uniquely enriched in the immortalized normal line.
In ACC and breast cancers, SOX10 expression negatively correlated with FOXA1, a cell identity marker and major regulator of the luminal breast subtype.
Recently, a groundbreaking study by the Lupien group has shown that risk-associated SNPs of breast cancer are enriched for FOXA1 binding sites, which influences the function of this transcription factor.
Our results indicate that ERα, FOXA1 and GATA3 contribute to the regulation of breast cancer susceptibility genes, which is consistent with the effects of anti-oestrogen treatment in breast cancer prevention, and suggest that fibroblast growth factor receptor 2 signalling has an important role in mediating breast cancer risk.
A role for FOXA1 in mediating breast cancer susceptibility at this locus is consistent with the finding that the FGFR2 risk locus primarily predisposes to estrogen-receptor-positive disease.