Crosstalk between adenosine receptor (A2A isoform) and ERα 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 ligandindependent 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• 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• signalling pathway. These results demonstrate cross-talk between A 2A AR and ER• that is involved in ethanol action. This could open new perspectives for the therapy of estrogen-dependent breast cancer.