17 β -Estradiol Activates HSF1 via MAPK Signaling in ER α -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 β -estradiol (E2), as well as xenoestrogen bisphenol A and ER α agonist propyl pyrazole triol, led to HSF1 phosphorylation on S326 in ER α positive but not in ER α -negative mammary breast cancer cells. Furthermore, we showed that MAPK signaling (via MEK1/2) but not mTOR signaling was involved in E2/ER α -dependent activation of HSF1. E2-activated HSF1 was transcriptionally potent and several genes essential for breast cancer cells growth and/or ER α 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 α and HSF1 signaling, which may support the growth of estrogen-dependent tumors.