Crosstalk between adenosine receptor (A(2A) isoform) and ER alpha mediates ethanol action in MCF-7 breast cancer cells
Fiche publication
Date publication
avril 2009
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ETIQUE Nicolas, Pr FLAMENT Stéphane, Dr GRILLIER-VUISSOZ Isabelle
Tous les auteurs :
Etique N, Grillier-Vuissoz I, Lecomte J, Flament S
Lien Pubmed
Résumé
Alcohol consumption increases the risk of breast cancer but the underlying mechanisms are not well understood. We have shown previously that ethanol activates ER signalling pathway in a cAMP/PKA-mediated ligand-independent manner. Since the activation of A(2A) adenosine receptor (A(2A)AR) by ethanol has been reported in other cell types, here we tested if cross-talk between this Gs-coupled receptor and ER alpha could be involved in ethanol effects in breast cancer cells. Our study shows that A(2A)AR is expressed and functional in the hormone-dependent breast cancer cell line MCF-7. Interestingly, activation of this receptor by the selective agonist CGS21680 stimulates the transcription of progesterone receptor, a well known estrogen target gene. CGS21680 also stimulates the pEREtkLuc reporter activity in transfected MCF-7 cells, an effect antagonized by the antiestrogen ICI182,780. Moreover, CGS21680 stimulates the proliferation of MCF-7 cells similarly to E-2. Finally, the A(2A)AR antagonist MSX-3 inhibits the ethanol-induced activation of ER alpha signalling pathway. These results demonstrate cross-talk between A(2A)AR and ER alpha that is involved in ethanol action. This could open new perspectives for the therapy of estrogen-dependent breast cancer.
Référence
Oncol Rep. 2009 Apr;21(4):977-81.