Induction of cyclooxygenase-2 expression by prostaglandin E2 stimulation of the prostanoid EP4 receptor via coupling to Gαi and transactivation of the epidermal growth factor receptor in HCA-7 human colon cancer cells
| Autor: | Sho Otake, Naofumi Seira, Kenji Yoshida, John W. Regan, Hiromichi Fujino, Toshihiko Murayama |
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| Rok vydání: | 2013 |
| Předmět: |
Transcriptional Activation
medicine.medical_specialty Dinoprostone Thromboxane receptor Transactivation chemistry.chemical_compound Phosphatidylinositol 3-Kinases Growth factor receptor Epidermal growth factor Internal medicine Cell Line Tumor medicine Enzyme-linked receptor Humans Epidermal growth factor receptor Extracellular Signal-Regulated MAP Kinases Pharmacology biology Chemistry Cell Membrane Prostanoid GTP-Binding Protein alpha Subunits Enzyme Activation ErbB Receptors Endocrinology Cyclooxygenase 2 Colonic Neoplasms Cancer research biology.protein Metalloproteases Intercellular Signaling Peptides and Proteins Tyrosine lipids (amino acids peptides and proteins) Signal transduction Receptors Prostaglandin E EP4 Subtype Heparin-binding EGF-like Growth Factor |
| Zdroj: | European journal of pharmacology. 718(1-3) |
| ISSN: | 1879-0712 |
| Popis: | Increased expressions of cyclooxygenase-2 (COX-2) and its downstream metabolite, prostaglandin E2 (PGE2), are well documented events in the development of colorectal cancer. Interestingly, PGE2 itself can induce the expression of COX-2 thereby creating the potential for positive feedback. Although evidence for such a positive feedback has been previously described, the specific E-type prostanoid (EP) receptor subtype that mediates this response, as well as the relevant signaling pathways, remain unclear. We now report that the PGE2 stimulated induction of COX-2 expression in human colon cancer HCA-7 cells is mediated by activation of the prostanoid EP4 receptor subtype and is followed by coupling of the receptor to Gαi and the activation of phosphatidylinositol 3-kinase. Subsequent activation of metalloproteinases releases membrane bound heparin-binding epidermal growth factor-like growth factor resulting in the transactivation of epidermal growth factor receptors and the activation of the extracellular signal-regulated kinases and induction of COX-2 expression. This induction of COX-2 expression by PGE2 stimulation of the prostanoid EP4 receptor may underlie the upregulation of COX-2 during colorectal cancer and appears to be an early event in the process of tumorigenesis. |
| Databáze: | OpenAIRE |
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