Expression of 5-oxoETE receptor in prostate cancer cells: critical role in survival.
Previously, we reported that metabolism of arachidonic acid through the 5-lipoxygenase (5-LOX) pathway plays an important role in the survival and growth of human prostate cancer cells. Inhibition of 5-LOX by pharmacological inhibitors triggers apoptosis in prostate cancer cells within hours of treatment, which is prevented by the metabolites of arachidonate 5-lipoxygenase, 5(S)-hydroxyeicosatetraenoic acid (5(S)-HETE), and its dehydrogenated derivative, 5-oxoeicosatetraenoic acid (5-oxoETE). These findings suggested that 5-lipoxygenase metabolites are critical survival factors of prostate cancer cells. However, molecular mechanisms by which 5(S)-HETE and its derivative 5-oxoETE exert their effects on prostate cancer cell survival are yet to be understood. Here, we report that human prostate cancer cells differentially express a G-protein-coupled 5-oxoETE receptor (5-oxoER) in them. Blocking expression of 5-oxoER by short-interfering RNA (siRNA) significantly reduced the viability of prostate cancer cells, suggesting that 5-oxoER is critical for prostate cancer cell survival, and that the 5-LOX metabolite, 5-oxoETE, controls survival of prostate cancer cells through its own G-protein-coupled receptor, 5-oxoER.
Sundaram
Sathish
S
Department of Urology, Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI 48202, USA.
Ghosh
Jagadananda
J
D000595:Amino Acid Sequence; D017209:Apoptosis; D001095:Arachidonic Acids / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D018055:Receptors, Eicosanoid / Q000235:genetics / Q000378:metabolism*
D001095:Arachidonic Acids; C504018:OXER1 protein, human; D034741:RNA, Small Interfering; D018055:Receptors, Eicosanoid; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid