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.
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.
Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer.
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.
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.
Functional Variant rs4442975 Modulating FOXA1 Binding Affinity Can Influence Bone Marrow Suppression during Neoadjuvant Chemotherapy for Luminal A Type Breast Cancer.
This study explored the FOXA1 relationship with luminal and basal breast cancer subtypes, proliferation markers, and survival in breast cancer patients who had received similar treatment.
Stable expression of FOXA1, but not ERα, reduced the expression of <i>IL6</i> in the FOXA1- and ERα-negative breast cancer MDA-MB-231 cells and TAM-R cells, without affecting the activation of the NF-κB signaling pathways.
The analysis revealed already well-established associations with XBP1 and FOXA1, but also identified a strong association with CT62, a potential immunotherapeutic target with few previous associations with breast cancer.
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 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.
Interdependency between these three factors in breast cancer and normal mammary development has been suggested, but the specific role for FOXA1 is not known.
In addition, the results are consistent with the notion that parity-associated epigenetic silencing of FOXA1 contributes to long-term attenuation of the estrogenic impact on breast cancer development.
The comparison of our signature with two pioneering signatures, the Sorlie's signature and PAM50, suggests a novel marker, FOXA1, in breast cancer classification.
FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding.
In normal breast tissue FOXA1 acts throughout mammary development; whereas in breast carcinoma its expression promotes luminal phenotype and correlates with good prognosis.
ABC successfully identifies previously characterized functional SNVs, such as the rs4784227breast cancer risk associated SNP that modulates the affinity of FOXA1 for the chromatin.
This is in line with other studies suggesting these SNPs as risk-associated polymorphisms which may lead to a change in the affinity of FOXA1, as a distal enhancer, to <i>TOX3</i> and thus change in <i>TOX3</i> expression, which can eventually affect the risk of breast cancer.
Analyses of an epigenetic switch involved in the activation of pioneer factor FOXA1 leading to the prognostic value of estrogen receptor and FOXA1 co-expression in breast cancer.