Heat Shock Factor 1 (HSF1) acquires transcriptional competence under 17b-estradiol in ERa-positive breast cancer cells [ChIP-seq]

Heat Shock Transcription Factor 1 (HSF1) is a well-known regulator of gene expression during acute environmental stress that enables the cells to survive. Its high level in estrogen receptor-positive breast cancer patients correlated with a worse prognosis. Here, we demonstrated that 17ß-estradiol (E2) as well as bisphenol A (BPA) and propyl pyrazole triol (PPT, ERa agonist) led to HSF1 phosphorylation on S326 in ERa positive mammary breast cancer cells, but not in ERa-negative ones. We showed that ERK1/2 signaling was involved in this process and down-regulation of ERa expression abrogated it. E2­activated HSF1 was transcriptionally potent. Chip-Seq and RNA-Seq analyses revealed that it could modulate the expression of several genes known to be essential for breast cancer cells growth and/or ERa action, i.e. HSPB8, LHX4, PRKCE, WWC1, and GREB1. Our findings indicate that a positive feedback loop between ERa and HSF1 signaling may exist which support the growth of estrogen-dependent tumors. Overall design: We sequenced DNA immunoprecipitated from wild type MCF7 cells using rabbit polyclonal anti-HSF1 antibodies. Cells were untreated (control), subjected to hyperthermia or stimulated using estrogen (17beta-estradiol) for indicated time. Six ChIP replicates were collected and pooled per each sequenced sample. Input samples were included as negative control (no DNA enrichment was observed in mock-IP samples).