INBIOMED   24026
INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Soluble guanylyl cyclase alpha1 subunit is a novel key mediator of proliferation in several estrogen-dependent human tumor cell lines
Autor/es:
GURRUCHAGA A; RICCI AG; CORDEIRO G; CABILLA JP; RONCHETTI SA; DUVILANSKI BH
Lugar:
Mar del Plata
Reunión:
Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016
Institución organizadora:
SAIC
Resumen:
The nitric oxide receptor soluble guanylyl cyclase (sGC) is a heterodimer composed by two subunits alpha and beta and catalyzes cGMP formation. We have shown that E2 exerts opposite effects on these sGC subunits, increasing both alpha1 (a1) levels and decreasing beta1 (b1) expression in vitro and in vivo. Besides, a1 increase has been strongly associated with cell proliferation and tumor progression in androgen-dependent tumor cell line LNCaP. On the other hand, b1 would be involved in cell cycle arrest and high levels of b1 are associated with better prognosis in breast cancer. The aim of the present work was to investigate the role of sGC a1 subunit in cell proliferation. Estrogen-responsive breast cancer MCF-7 and endometrial tumor cell line ECC-1 were used. a1 expression was silenced through siRNA specific sequences using scramble sequences as control. Cells were incubated with or without 1 nM E2 for 48 h. a1, b1 and PCNA protein levels were measured by western blot. Cell proliferation was assessed by BrdU incorporation. a1 knock-down reduced PCNA levels in ECC-1 and MCF-7 (50% and 70% of decrease vs. respective control). Surprisingly, a1 siRNA-transfected cells showed a significantly augment in b1 protein levels (ECC-1: 2.5, MCF-7: 3.6 fold-increase). Moreover, a1 silencing reduced E2-stimulated cell proliferation in ECC-1 cells evidenced by a decrease in PCNA protein levels (% of C, E2: 275.9±2**, a1 siRNA: 60±5*, a1 siRNA: 69.2±6*, *p