Expression of 5-oxoETE receptor in prostate cancer cells: critical role in survival.

Abstract

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.

• Authors: Sathish Sundaram, Jagadananda Ghosh
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 339 Issue 1 Pg. 93-8 (Jan 06 2006) ISSN: 0006-291X [Print] United States
• PMID: 16289380 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Arachidonic Acids
• OXER1 protein, human
• RNA, Small Interfering
• Receptors, Eicosanoid
• 5-oxo-6,8,11,14-eicosatetraenoic acid

Topics

• Amino Acid Sequence
• Apoptosis
• Arachidonic Acids (metabolism)
• Cell Line, Tumor
• Cell Survival
• Humans
• Male
• Molecular Sequence Data
• Neoplasms, Hormone-Dependent (metabolism, pathology)
• Prostatic Neoplasms (metabolism, pathology)
• RNA, Small Interfering (genetics)
• Receptors, Eicosanoid (genetics, metabolism)