20-HYDROXYEICOSATETRAENOIC ACID (20- HETE) PROMOTES A MALIGNANT PHENOTYPE IN HUMAN CASTRATION-RESISTANT PROSTATECANCER CELLS THROUGH STIMULATION OF THE G PROTEIN-COUPLED RECEPTOR GPR75.

COLOMBERO C; FALCK J.; CÁRDENAS, SOFIA; 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-Hydroxyeicosatetraenoic acid (20-HETE), the product of 20-hydroxylation of arachidonic acid bycytochrome P450 isoforms (CYP4F2 and CYP4A11), has a role inthe oncogenesis of several human tumors. Recently, the GPR75receptor has been identified as the target for 20-HETE. We haveshown that androgen independent prostate cancer cells (PC-3)express GPR75. The aim of this study was to assess in vitro if20-HETE/GPR75 modify the metastatic features of PC-3 cells.Cells were incubated with 20-HETE or its stable analog 5,14-HEDGE (both 0.1 nM) in the presence or absence of two differentantagonists of the 20-HETE receptor, AAA or 19-HEDE (both 5 or10 uM). The following assays were performed: e-cadherin andvimentin protein expression (epithelial-mesenchymal transition),zymography (release of matrix metalloproteinase-2 (MMP-2)),immunofluorescence and p-FAK (changes of cytoskeleton),scratch wound healing (migration), and soft agar colonyformation (anchorage-independent growth). Results wereanalyzed using one-way ANOVA followed by Dunnet?s. 20-HETE(24 h) increased by 150 % the expression of vimentin(p