17β-Estradiol Activates HSF1 via MAPK Signaling in ERα-Positive Breast Cancer Cells

Heat Shock Factor 1 (HSF1) is a key regulator of gene expression during acute environmental stress that enables the cell survival, which is also involved in different cancer-related processes. A high level of HSF1 in estrogen receptor (ER)-positive breast cancer patients correlated with a worse prognosis. Here we demonstrated that 17 beta-estradiol (E2), as well as xenoestrogen bisphenol A and ER alpha agonist propyl pyrazole triol, led to HSF1 phosphorylation on S326 in ER alpha positive but not in ER alpha-negative mammary breast cancer cells. Furthermore, we showed that MAPK signaling (via MEK1/2) but not mTOR signaling was involved in E2/ER alpha-dependent activation of HSF1. E2 activated HSF1 was transcriptionally potent and several genes essential for breast cancer cells growth and/or ER alpha action, including HSPB8, LHX4, PRKCE, WWC1, and GREB1, were activated by E2 in a HSF1-dependent manner. Our findings suggest a hypothetical positive feedback loop between E2/ER alpha and HSF1 signaling, which may support the growth of estrogen-dependent tumors.