Adrenergic receptors in breast cancer: differential effects of alpha2A and 2C-adrenergic receptor expression on tamoxifen sensitivity in stably transfected luminal MCF-7 cells.

RIVERO, E.M.; BRUZZONE, A.; BRUQUE C.D.; PEREZ-PIÑERO C.; APARICIO E.; RODRIGUEZ M.S.; LUTHY, I.

Mar del Plata

Congreso; Congreso Conjunto de Sociedades Biomédicas; 2019

SAIC

Breast cancer is the most frequently diagnosed and leading cause of cancer death among women worldwide .Epinephrine and norepinephrine, released during stress, bind to 9 different adrenoceptors.Our group has already described (SAIC 2015, poster 660) by in silico analysis in a great database that patients with high expression of Alpha2A-adrenoceptors(A2A-AR) have better disease-free survival than those with lower expression, mainly in luminal tamoxifen-treated ones. Contrarily, a high expression of Alpha2C-AR was associated with worse outcome in luminal B but not in luminal A patients. The aim of the present work was to study the sensibility of tamoxifen on A2A or A2C-AR-overexpressing cells.The human luminal breast cancer MCF-7 cells were stably transfected with α2A or α2C-AR or the empty vector. The expression of A2-AR and Estrogen Receptor Alpha (ER) was measured by RT-qPCR, the sensitivity to tamoxifen by tritiated thymidine incorporation and ER, progesterone receptor and pERK relative to ERK ,by Western Blot. They were all performed in the absence of adrenergic stimulation because catecholamines released during stress bind to all receptors and no specific ligand for individual A2-AR exists yet.We successfully over expressed alpha2A and alpha2C on MCF-7 cells: 65% (A2A) and 28 % (A2C) increase compared with empty vector (pCDNA, p