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KMID : 0603520030080040251
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Journal of Korean Association of Cancer Prevention
2003 Volume.8 No. 4 p.251 ~ p.260
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Role of Cyclooxygenase-2 and Its Products in the Regulation of Cell Growth
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Na Hye-Kyung
Surh Young-Joon
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Abstract
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Arachidonic acid is metabolized to prostaglandin H2 by cyclooxygenase (COX). Prostaglandins exert diverse physiological actions to maintain mucosal integrity, regulation of secretion and motility. Among the various COX products, abnormally elevated levels of prostaglandin E2 (PGE2) have been often observed in various types of human cancers. Moreover, COX-2, the inducible COX isozyme, has been implicated in pathogenesis of various malignancies. PGE2 generated by COX-2 increased the cellular cAMP level via EP2, a cell-surface receptor of this prostaglandin, and further stimulates expression of COX-2. PGE2 activates the epidermal growth factor receptor-hepatocyte growth factor receptor- j3-catenin-uPAR signaling pathway, thereby augmenting invasiveness and metastasis of cancer cells. In contrast, 15-deoxy-Q 12´14PGJ2 (15d-PGJ2), another COX-2 metabolite and a natural ligand for the peroxisome proliferator-activated receptors 7 (PPAR y), causes apoptosis, inhibition of cell growth, anti-inflammation, and cytoprotection. 15d-PGJ2 and some synthetic PPAR y ligands also regulate the expression of COX-2 through peroxisome proliferator response element, which is accompanied by induction of apoptosis. Therefore, the physiological and toxicological effects associated with induction of COX-2 expression depend on types of cells and stimuli.
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KEYWORD
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Cyclooxygenase-2, 15-deoxy-Δ^(12, 14)prostaglandin J_(2) PGE_(2), Cell growht/Death, Peroxisome proliferator-activated receptor γ ligands
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