The Expression Of Four Kinds Of Prostaglandin E2 Receptors And Their Intracellular Location In Human Liver Cancer Cells

Background:Recently, a heightened interest in the role of cyclooxyenase-2 (COX-2)-derived prostaglandin E2 (PGE2) in neoplasia has emerged. Some studies have demonstrated COX-2/PGE2-induced stimulation of neoplastic and non- neoplastic cell growth, whereas other investigators' results have suggested antiproliferative effects of PGE2. As we known, PGE2 mediates its physiological effects by interactions with a subfamily of G-protein-coupled receptors known as EP receptors. These receptors consist of four primary subtypes named EP1, EP2, EP3 and EP4. The EP1 receptors are known to couple to Gq, elevate intracellular Ca²⁺ concentration, and activate protein kinase C (PKC). EP3 receptors have been found to couple to Gi and inhibit intracellular cyclic 3,5-adenosine monophosphate(cAMP) formation. Both EP2 and EP4 receptors are initially characterized as coupling to Gs, increasing intracellular cAMP formation, and inducing the activation of cAMP-dependent protein kinase A(PKA). Over the last few years, it is reported that EP4 receptors signaling also involves the activation of phosphatidylinositol 3-kinase (PI3K) and serine/threonine protein kinase B (Akt). Based on these explanations about EP receptors, it is suggested that activation of EP1,...