Crosstalk between adenosine receptor (A2A isoform) and ERalpha mediates ethanol action in MCF-7 breast cancer cells.
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 A2A adenosine receptor (A2AAR) by ethanol has been reported in other cell types, here we tested if cross-talk between this Gs-coupled receptor and ERalpha could be involved in ethanol effects in breast cancer cells. Our study shows that A2AAR 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 E2. Finally, the A2AAR antagonist MSX-3 inhibits the ethanol-induced activation of ERalpha signalling pathway. These results demonstrate cross-talk between A2AAR and ERalpha that is involved in ethanol action. This could open new perspectives for the therapy of estrogen-dependent breast cancer.
Etique
Nicolas
N
EA 3442 Aspects Cellulaires et Moléculaires de la Reproduction et du Développement, Nancy-Université, Université Henri Poincaré, Faculté des Sciences, 54506 Vandoeuvre-lès-Nancy, France.
Grillier-Vuissoz
Isabelle
I
Lecomte
Julie
J
Flament
Stephane
S
D001943:Breast Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000502:physiology*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000628:therapy; D020239:Receptor Cross-Talk / Q000502:physiology*; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D043705:Receptor, Adenosine A2A; D000431:Ethanol