dc.creator | Cardenas, Sofía | |
dc.creator | Colombero, Cecilia | |
dc.creator | Panelo, Laura Carolina | |
dc.creator | Dakarapu, Rambabu | |
dc.creator | Falck, John | |
dc.creator | Costas, Monica Alejandra | |
dc.creator | Nowicki, Susana | |
dc.date.accessioned | 2022-04-01T11:57:45Z | |
dc.date.accessioned | 2022-10-15T10:26:49Z | |
dc.date.available | 2022-04-01T11:57:45Z | |
dc.date.available | 2022-10-15T10:26:49Z | |
dc.date.created | 2022-04-01T11:57:45Z | |
dc.date.issued | 2019 | |
dc.identifier | 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; Reunión anual de las Sociedades de Biociencia; Mar del Plata; Argentina; 2019; 82-82 | |
dc.identifier | 0025-7680 | |
dc.identifier | http://hdl.handle.net/11336/154163 | |
dc.identifier | 1669-9106 | |
dc.identifier | CONICET Digital | |
dc.identifier | CONICET | |
dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/4375516 | |
dc.description.abstract | 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<0.01 for NF-kB, and p<0.001 for EGFR and AKT, n=3), and this was inhibited by AAA (vs 20-HETE alone, p<0.05 for NF-kB, p<0.01 for AKT and p<0.001 for EGFR). AAA alone increased p-38 phosphorylation by 248% (p<0.001 vs control, n=3). 20-HETE (1 h) induced the translocation of p-AKT to the nuclei (p<0.001, n=3) and promoted the redistribution of PKCa out of the nuclei (p<0.05, n=3) to the plasma membrane (p<0.001). Both effects were inhibited by AAA (vs 20-HETE, p<0.01 for AKT and p<0.05 for PKCa). AAA alone reduced the nuclear signal of p-AKT and NF-kB usually activated in tumoral cells (p<0.001 for both, n=3). Additionally, 20-HETE (12 h) increased by 150% the protein expression of Hic-5 (p<0.0001, n=5) and this was abolished by AAA (p<0.001).Our results show that 20-HETE modulates signaling pathways known to be deregulated in malignant cells through the GPR75-axis. | |
dc.language | spa | |
dc.publisher | Fundación Revista Medicina | |
dc.relation | info:eu-repo/semantics/altIdentifier/url/https://medicinabuenosaires.com/revistas/vol79-19/s4/vol79_s4.pdf | |
dc.rights | https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.source | Medicina (Buenos Aires) | |
dc.subject | CANCER DE PROSTATA | |
dc.subject | EICOSANOIDES | |
dc.subject | SEÑALES INTRACELULARES | |
dc.subject | RECEPTOR GPR75 | |
dc.title | 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 | |
dc.type | info:eu-repo/semantics/publishedVersion | |
dc.type | info:eu-repo/semantics/conferenceObject | |
dc.type | info:ar-repo/semantics/documento de conferencia | |