Chapter

Eicosanoids and other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 3

Volume 407 of the series Advances in Experimental Medicine and Biology pp 61-66

Function and Regulation of Prostaglandin Synthase-2

  • Harvey R. HerschmanAffiliated withDepartments of Biological Chemistry and Pharmacology, Molecular Biology Institute, and Laboratory of Structural Biology and Molecular Medicine, University of California, Los Angeles
  • , Srinivasa T. ReddyAffiliated withDepartments of Biological Chemistry and Pharmacology, Molecular Biology Institute, and Laboratory of Structural Biology and Molecular Medicine, University of California, Los Angeles
  • , Weilin XieAffiliated withDepartments of Biological Chemistry and Pharmacology, Molecular Biology Institute, and Laboratory of Structural Biology and Molecular Medicine, University of California, Los Angeles

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Abstract

Our laboratory has identified cDNAs for a number of genes that are induced in fibroblasts in response to treatment with tumor promoters and growth factors (1). One of these genes encodes the inducible form of prostaglandin synthase (2), now known as PGS-2 or cyclooxygenase 2 (COX-2). We demonstrated that the product of the PGS-2 gene has both cyclooxygenase and hydroperoxidase activities (3); that PGS-2 is a functional prostaglandin synthase. At about the time that we identified the cDNA that encoded PGS-2 in mitogen/tu-mor promoter treated murine fibroblasts, Xie et al (4) demonstrated that chick embryo fibroblasts transformed by the Rous sarcoma virus also expressed a cDNA that encoded a protein with strong sequence homology to rodent and mammalian prostaglandin synthase proteins. Although Xie et al (4) suggested the v-src-induced PGS might be a previously unde-scribed isoform of prostaglandin synthase, they could not be certain of this conclusion, since the chicken homologue of prostaglandin synthase had not been described. The laboratories of Donald Young and Rodregio Bravo also cloned the murine PGS-2 cDNA, at about the same time. Independent biochemical and immunochemical studies suggested the existence of a hor-mone-inducible form of PGS in rat ovarian granulosa cells. Subsequently, the human and rat PGS-2 cDNAs were cloned by several laboratories.