STAT3 and GR cooperate to drive basal-like triple negative breast cancer gene expression and proliferation

Breast cancers can be divided into subtypes with different prognoses and treatment responses based on global gene expression differences. This study utilized integrated analysis of DNA methylation, chromatin accessibility, transcription factor binding, and gene expression in large collections of breast cancer cell lines and patient tumors to identify transcription factors responsible for the basal-like gene expression program. The results of this study indicate that glucocorticoid receptor (GR) and signal transducer and activator of transcription 3 (STAT3) bind to the same genomic regulatory regions that are specifically open and unmethylated in basal-like breast cancer. These transcription factors cooperate to regulate expression of hundreds of genes in the basal-like gene expression signature and these downstream genes are associated with poor prognosis in patients. Transcription factor ChIP-seq for GR and STAT3 was performed in TNBC cell lines, SUM159, MDA-MB-231, HCC1937, HCC70, HCC1187, and luminal cell lines MDA-MB-361, BT-474, MDA-MB-453, and MCF-7. STAT3 and GR ChIP-seq was performed after 1hr vehicle control induction (ethanol) and 100nM Dexamethasone induction respectively.