Breast cancer metastases (n = 164) from various anatomical sites were retrospectively analyzed by immunohistochemistry for FOXA1, Nestin and GATA3 expression.
FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding.
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.
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 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.
ABC successfully identifies previously characterized functional SNVs, such as the rs4784227breast cancer risk associated SNP that modulates the affinity of FOXA1 for the chromatin.
Altered FOXA1 levels contribute to endocrine-resistant breast cancer, where it maintains ER-chromatin interactions, even in contexts in which cells are refractory to ER-targeted drugs.
Although AR and FOXA1 bound the UGT promoters in AR-positive/ERα-negative breast cancer cell lines, androgen treatment did not influence basal transcription levels.
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.
Analysis of breast cancer gene expression data indicates that HOTAIR is co-expressed with FOXA1 and FOXM1 in HER2-enriched tumours, and these factors enhance the prognostic power of HOTAIR in aggressive HER2+ breast tumours.
Biological assays indicated that the germline G>T variation at rs6506689 creates a FOXA1-binding site and up-regulates the expression of RAB31, thus playing an important role in the development of BC.
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.