CEDIE   05498
CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Intracellular signaling pathways triggered by the stimulation of the G-coupled Protein Receptor GPR75 by 20-hydroxyeicosatetraenoic acid (20-HETE) in androgen independent prostate cancer cells.
Autor/es:
CARDENAS S; COLOMBERO C; FALCK J; DAKARAPU R; PANELLO LC; NOWICKI S; COSTAS MA
Lugar:
Mar del Plata
Reunión:
Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2019
Institución organizadora:
Sociedad Argentina de Investigación Clínica
Resumen:
20-HETE, the product of 20-hydroxylation of arachidonic acid by cytochrome P450 isoforms (CYP4F2 and CYP4A11), has a role in the oncogenesis of several human tumors. Recently, the GPR75 receptor has been identified as the target for 20-HETE. We have shown that androgen independent prostate cancer cells (PC-3) express GPR75. The aim of this study was to identify intracellular signaling molecules activated upon GPR75 stimulation by 20-HETE in PC-3 cells.Cells were incubated with 20-HETE (0.1 nM) in the presence or absence of the antagonist of the 20-HETE receptor, AAA (5 or 10 uM). Protein expression of the inducible focal adhesion protein Hydrogen Peroxide Inducible Clone-5 (HIC-5), the phosphorylated and total form of NF-kB, AKT, p38 MAP-Kinase (p38) and EGFR were assessed by western blot. Intracellular localization of p-AKT, NF-kB and PKCa were determined by immunofluorescence and subcellular fractionation. Migration of PC-3 cells incubated with diferentes inhibitors were evaluated by scratch wound healing assay. Results were analyzed using one-way ANOVA followed by Dunnet?s.Incubation with 20-HETE (2 h) increased the phosphorylation of EGFR, NF-kB and AKT by 146, 172 and 219%, respectively (vs control, p