Combined estrogenic and anti-estrogenic properties of estetrol on breast cancer may provide a safe therapeutic window for the treatment of menopausal symptoms
[en] Increased risk of breast cancer is a critical side effect associated with the use of a menopausal hormone therapy (MHT). Estetrol (E4) is a natural estrogen produced by the human fetal liver and is a promising compound for clinical use in MHT. However, its impact on breast cancer is controversial and poorly defined. In this preclinical study, we show that E4 acts as a weak estrogen by stimulating the growth of hormone-dependent breast cancer only at concentrations exceeding menopausal therapeutic needs. E4 presents also an antitumor activity by decreasing the strong proliferative effect of estradiol (E2). While estrogen receptor alpha (ERα) is the predominant receptor mediating its effects, the dual weak-estrogenic/anti-estrogenic feature of E4 results from differential signaling pathways activation. Both nuclear and rapid extra-nuclear signaling pathway are necessary for a complete estrogenic effect of E4. However, the antitumor action of E4 is not due to a capacity to antagonize E2-induced nuclear activity. Altogether, our results highlight that E4 has a limited impact on breast cancer and may offer a safe therapeutic window for the treatment of menopausal symptoms.
Disciplines :
Oncology
Author, co-author :
Gérard, Céline ; Université de Liège > Département des sciences cliniques > LBTD/GIGA-cancer
Mestdagt, Mélanie; Université de Liège - ULiège > Département des Sciences Cliniques > LBTD/GIGA-cancer
Tskitishvili, Ekaterine ; Université de Liège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Communal, Laudine; Paris Descartes University, Hôpitaux Universitaires > Gynaecological Endocrinology Unit
Gompel, Anne; Université Pierre et Marie Currie - Paris 6 - UPMC > INSERM U938
Silva, Elisabete; Brunel University London > Institute of Environment, Health and Societies
Noël, Agnès ; Université de Liège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme/GIGA-cancer
Foidart, Jean-Michel ; Université de Liège > Département des sciences cliniques > Gynécologie - Obstétrique
Pequeux, Christel ; Université de Liège > Département des sciences biomédicales et précliniques > LBTD/GIGA-cancer
Language :
English
Title :
Combined estrogenic and anti-estrogenic properties of estetrol on breast cancer may provide a safe therapeutic window for the treatment of menopausal symptoms
Publication date :
19 May 2015
Journal title :
Oncotarget
eISSN :
1949-2553
Publisher :
Impact Journals, Albany, United States - New York
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique Région Wallonne: Direction générale opérationnelle de l'Economie, de l'Emploi & de la Recherche (DGO6)
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