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Open AccessArticle

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

Maria Sklodowska-Curie Institute – Oncology Center, Gliwice Branch, 44-101 Gliwice, Wybrzeże Armii Krajowej 15, Poland
Department of Clinical Science, University of Bergen, Postboks 7800, 5020 Bergen, Norway
Laboratory of Molecular Neurobiology, Neurobiology Center, Nencki Institute of Experimental Biology, PAS, 3 Pasteur Street, 02-093 Warsaw, Poland
Authors to whom correspondence should be addressed.
These authors contributed equally.
Cancers 2019, 11(10), 1533;
Received: 21 September 2019 / Revised: 5 October 2019 / Accepted: 7 October 2019 / Published: 11 October 2019
(This article belongs to the Special Issue New Insights into Breast and Endometrial Cancer)
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 17β-estradiol (E2), as well as xenoestrogen bisphenol A and ERα agonist propyl pyrazole triol, led to HSF1 phosphorylation on S326 in ERα positive but not in ERα-negative mammary breast cancer cells. Furthermore, we showed that MAPK signaling (via MEK1/2) but not mTOR signaling was involved in E2/ERα-dependent activation of HSF1. E2­activated HSF1 was transcriptionally potent and several genes essential for breast cancer cells growth and/or ERα 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/ERα and HSF1 signaling, which may support the growth of estrogen-dependent tumors. View Full-Text
Keywords: bisphenol A; estrogen; Heat Shock Factor 1; MEK1/2; xenoestrogen bisphenol A; estrogen; Heat Shock Factor 1; MEK1/2; xenoestrogen
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Vydra, N.; Janus, P.; Toma-Jonik, A.; Stokowy, T.; Mrowiec, K.; Korfanty, J.; Długajczyk, A.; Wojtaś, B.; Gielniewski, B.; Widłak, W. 17β-Estradiol Activates HSF1 via MAPK Signaling in ERα-Positive Breast Cancer Cells. Cancers 2019, 11, 1533.

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