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Estrogen receptor signaling as a target for novel breast cancer therapeutics.
Renoir J.-M., Marsaud V., Lazennec G.
Biochemical Pharmacology 85, 4 (2013) 449-65 - http://www.hal.inserm.fr/inserm-00758201
(23103568)
Estrogen receptor signaling as a target for novel breast cancer therapeutics.
Jack-Michel Renoir () 1, Véronique Marsaud2, Gwendal Lazennec3
1 :  Recepteurs et Signalisation des Interleukines
INSERM : U749 – Université Paris XI - Paris Sud – Institut Gustave Roussy
Pavillon de Recherche 2 - Niveau 3 39 rue Camille Desmoulins 94805 Villejuif Cedex
France
2 :  Signalisation normale et pathologique de l'embryon aux thérapies innovante des cancers
INSERM : U1021 – Institut Curie – CNRS : UMR3347
Orsay
France
3 :  Cellules souches mésenchymateuses, environnement articulaire et immunothérapies de la polyarthrite rhumatoide
INSERM : U844 – IFR3 – Université Montpellier I
Hôpital Saint Eloi - Bâtiment INM 80 rue Augustin Fliche BP 74103 - 34091 Montpellier cedex 5
France
new targets in estradiol receptor-positive breast cancers
In breast cancer (BC) epithelial cells, the mitogenic action of estradiol is transduced through binding to two receptors, ERα and ERβ, which act as transcription factors. Anti-estrogens (AEs) and aromatase inhibitors (AIs) are used clinically to arrest the estrogen-dependent growth of BC. In the case of AE or AI resistance, Herceptin or lapatinib may be used to inhibit growth factors. Estrogen effects are mediated not only through nuclear ERs but also through cytoplasmic/membrane ERs and G-protein-coupled ERs. These estrogen-binding systems associate with various proteins that direct cell cycle signaling, proliferation and survival. The partners of nuclear ER include SRC1-3, HDACs and ERβ itself as well as newly identified proteins, such as E6-AP, LKB1, PELP1, PAX-2 and FOXA1. The partners of extra-nuclear ERα include PI3K and the tyrosine kinase Src. These various factors are all potential targets for therapeutic intervention. In addition, BC proliferation is enhanced by insulin and EGF, which stimulate signaling through the MAPK and PI3K/AKT pathways by activation of the IGF-1R and EGFR axes, respectively. These pathways are tightly interconnected with ER-activated signaling, and membrane ERα forms complexes with Src and PI3K. Chemokine-mediated signaling also modulates the estrogen response. Inhibiting these pathways with specific inhibitors or activating some of the pathways by gene manipulation may be therapeutically valuable for arresting BC cell cycle progression and for inducing apoptosis to antagonize hormone-resistance. Here, we review some newly identified putatively targetable ER partners and highlight the need to develop tumor-targeting drug carrier systems affecting both the tumor cells and the tumor environment.
Sciences du Vivant/Cancérologie
Anglais
1873-2968

Articles dans des revues avec comité de lecture
10.1016/j.bcp.2012.10.018
Biochemical Pharmacology (Biochem Pharmacol)
Publisher Elsevier
ISSN 0006-2952 
internationale
15/02/2013
24/10/2012
85
4
449-65

Antineoplastic Agents – Breast Neoplasms – Female – Humans – Receptors – Estrogen – Signal Transduction
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