Beta adrenergic action on human breast cancer cell lines

PEREZ PIÑERO CECILIA; CASTILLO LILIAN F.; BRUZZONE ARIANA; LUTHY ISABEL A.

Orlando, FL

Congreso; 102nd Annual Meeting American Association for Cancer Research; 2011

American Association for Cancer Research

Breast cancer, the most frequent cancer among women in the majority of countries, is also a stressful disease. The principal effectors of the stress system include the epinephrine (EPI) and norepinephrine which bind to α1-, α2- and β-adrenoceptors (AR). We have described α2-AR in human tumor and non-tumor breast cell lines, associated with increased cell proliferation and tumor growth. We have also studied the effect of β-AR agonists and antagonists in different breast cancer experimental models. When animals were treated with the agonist isoproterenol (ISO) and/or salbutamol (SALB), tumor growth was significantly reduced correlating with Erk 1/2 phosphorylation status in whole protein tumor samples by Western blotting. The aims of the present work were: to assess the expression of β2-AR in human breast cancer cell lines (IBH-4, IBH-6,MDA-MB-231, MCF-7, among others) by RT-PCR and immunofluorescence (IF) techniques; to study the biological effect of β-AR agonists by means of proliferation assays and compare these results with the effect of the natural agonist (EPI); to find out the signaling pathways involved in reduced Erk phosphorylation induced by β-AR stimulation. β2-AR expression was detected by RT-PCR, using GAPDH as a control. A positive staining was seen in all cells by IF. After the incubation of the cells with increasing doses (from 10-13M to 10-6M) of the β-AR agonist (ISO or SALB), a significant reduction in [3H]-thymidine incorporation to the cells nuclei was observed as compared to control values (expressed as percentage of control incorporation). IBH-4: ISO 0.1μM, 75.87±8.49% vs control 100±7.18% p