title: OXER1, a G protein-coupled oxoeicosatetraenoid receptor, mediates the survival-promoting effects of arachidonate 5-lipoxygenase in prostate cancer cells.
abstract: Inhibition of 5-Lox induces apoptosis in prostate cancer cells by inactivating PKCε which is prevented by 5-oxoETE, and activators of PKCε prevent 5-Lox inhibition-induced apoptosis, suggesting that 5-Lox metabolites exert survival signaling via PKCε. However, mechanisms by which 5-Lox metabolites activate PKCε are not understood yet. We found that prostate cancer cells express high levels of OXER1, a G protein-coupled 5-oxoETE receptor, which delivers signal by generating diacyl-glycerol through phospholipase C-beta. Interestingly, we found that U73122, an inhibitor of PLC-beta, interrupts the apoptosis-preventing effect of 5-oxoETE, and exogenous diacyl-glycerol effectively prevents 5-Lox inhibition-induced apoptosis, suggesting that 5-oxoETE signals via OXER1 to promote prostate cancer cell survival.
authors: Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI 48202, USA.
authors: Sivalokanathan
authors: S
authors: Sarveswaran
authors: Jagadananda
authors: J
authors: Ghosh
mesh_terms: D017209:Apoptosis; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D008297:Male; D054799:Phospholipase C beta / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D018055:Receptors, Eicosanoid / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D004963:Estrenes; C504018:OXER1 protein, human; D011760:Pyrrolidinones; D018055:Receptors, Eicosanoid; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D001094:Arachidonate 5-Lipoxygenase; D051744:Protein Kinase C-epsilon; D054799:Phospholipase C beta
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