GSE104399
Characterizing steroid hormone receptor chromatin binding landscapes in male and female breast cancer
Male breast cancer (MBC) is rare and poorly characterized. Like the female counterpart, most MBCs are hormonally driven, but resistance to hormonal treatment is common. The pan-hormonal action of steroid hormonal receptors including Estrogen Receptor alpha (ERa), Androgen Receptor (AR), Progesterone Receptor (PR) and Glucocorticoid Receptor (GR) in this understudied tumor type remains wholly unexamined. This pioneering study reveals genomic cross-talk of steroid hormone receptor action and interplay in human tumors, here in the context of MBC, in relation to patient outcome.  Using chromatin immunoprecipitation coupled with massively-parallel sequencing (ChIP-seq), we characterized human MBCs for epigenetic make-up of hormonal regulation in human tumors, revealing genome-wide chromatin binding landscapes of ERa, AR, PR and GR, along with pioneer factor FOXA1 and enhancer-enriched histone mark H3K4me1. These data were integrated with transcriptomics analyses to reveal gender-selective and genomic location-specific hormone receptor action, that are associated with survival in MBC patients. Overall design: Binding of steroid hormone receptors (ER, AR, PR, GR) together with pioneer factors (FOXA1, GATA3) and a histone mark (H3K4me1) profiled in subsets of 30 males and 8 females breast tumors, and MCF-7 by ChIP-seq (Chromatin Immunoprecipitation followed by deep sequencing).