OXER1, a G protein-coupled oxoeicosatetraenoid receptor, mediates the survival-promoting effects of arachidonate 5-lipoxygenase in prostate cancer cells

Cancer Lett. 2013 Aug 9;336(1):185-95. doi: 10.1016/j.canlet.2013.04.027. Epub 2013 May 2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Apoptosis
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Cell Line, Tumor
  • Cell Survival
  • Estrenes / pharmacology
  • Humans
  • Male
  • Phospholipase C beta / metabolism
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Protein Kinase C-epsilon / metabolism
  • Pyrrolidinones / pharmacology
  • Receptors, Eicosanoid / metabolism*
  • Signal Transduction
  • Time Factors

Substances

  • Estrenes
  • OXER1 protein, human
  • Pyrrolidinones
  • Receptors, Eicosanoid
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Arachidonate 5-Lipoxygenase
  • Protein Kinase C-epsilon
  • Phospholipase C beta