INTRACELLULAR SIGNALING PATHWAYS TRIGGERED BY THE STIMULATION OF THE GCOUPLED PROTEIN RECEPTOR GPR75 BY 20- HYDROXYEICOSATETRAENOIC ACID (20-HETE) IN ANDROGEN INDEPENDENT PROSTATE CANCER CELLS.

COLOMBERO, CECILIA; FALCK J.; DAKARAPU. R.; NOWICKI S; PANELO L.C.; COSTAS M. A.

Mar Del Plata

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

Sociedad Argentina de Investigación Clinica

20-HETE, the product of 20-hydroxylationof arachidonic acid by cytochrome P450 isoforms (CYP4F2 andCYP4A11), has a role in the oncogenesis of several humantumors. Recently, the GPR75 receptor has been identified as thetarget for 20-HETE. We have shown that androgen independentprostate cancer cells (PC-3) express GPR75. The aim of thisstudy was to identify intracellular signaling molecules activatedupon GPR75 stimulation by 20-HETE in PC-3 cells. Cells wereincubated with 20-HETE (0.1 nM) in the presence or absence ofthe antagonist of the 20-HETE receptor, AAA (5 or 10 μM).Protein expression of the inducible focal adhesion proteinHydrogen Peroxide Inducible Clone-5 (HIC-5), thephosphorylated and total form of NF-kB, AKT, p38 MAP-Kinase(p38) and EGFR were assessed by Western blot. Intracellularlocalization of p-AKT, NF-kB and PKCa were determined byimmunofluorescence and subcellular fractionation. Results wereanalyzed using one-way ANOVA followed by Dunnet?s. Incubationwith 20-HETE (2 h) increased the phosphorylation of EGFR, NFkBand AKT by 146, 172 and 219 %, respectively (vs. control,p