5(S)-Hydroxy-6,8,11,14-E, Z, Z, Z-eicosatetraenoate stimulates PC3 cell signaling and growth by a receptor-dependent mechanism

• Published in: Cancer research (Chicago, Ill.) Ill.), 2002-12, Vol.62 (23), p.6817-6819
• Main Authors: O'FLAHERTY, Joseph T, ROGERS, Leann C, CHADWELL, Brad A, OWEN, John S, RAO, Anurada, CRAMER, Scott D, DANIEL, Larry W
• Format: Article
• Language: English
• Subjects: Benzoquinones - pharmacology; Biological and medical sciences; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Fundamental and applied biological sciences. Psychology; GTP-Binding Proteins - physiology; Humans; Hydroxyeicosatetraenoic Acids - antagonists & inhibitors; Hydroxyeicosatetraenoic Acids - pharmacology; Hydroxyeicosatetraenoic Acids - physiology; Indoles - pharmacology; Male; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Molecular and cellular biology; Pertussis Toxin - pharmacology; Phosphorylation - drug effects; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - pathology; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Receptors, Eicosanoid - metabolism; Receptors, Eicosanoid - physiology; Stimulation, Chemical; Tumor Cells, Cultured
• ISSN: 0008-5472; 1538-7445

5(S)-Hydroxy-6,8,11,14-E,Z,Z,Z-eicosatetraenoate (5-HETE) causes PC3 cells to grow by an unknown mechanism. We find that it also induces the cells to activate extracellular signal-regulated kinases and Akt. Pertussis toxin inhibits both responses. 5-HETE, 5-oxo-6,8,11,14-E,Z,Z,Z-eicosatetraenoate, and 5-oxo-15-hydroxy-eicosatetraenoate are known to stimulate leukocytes by a receptor coupled to pertussis toxin-sensitive G proteins. Their respective relative potencies in leukocytes are 1, 10, and 3. In PC3 cells, however, these values are 10, 1, and 0. PC3 cells, we propose, express a non-leukocyte-type, G protein-coupled, 5-HETE receptor. This novel receptor and the extracellular signal-regulated kinase and Akt pathways it recruits may contribute to the progression of prostate adenocarcinoma.