Cyclooxygenase 2: from inflammation to carcinogenesis.
Cyclooxygenase (COX) is the rate-limiting enzyme in the conversion of arachidonic acid to prostanoids. Two COX isoforms have been cloned, of which COX-1 is constitutively expressed, while the expression of COX-2 is low or nondetectable in most tissues, but can be readily induced in response to cell activation by cytokines, growth factors and tumour promoters. Thus, COX-1 is considered a housekeeping gene and thought to be responsible for the synthesis of prostanoids involved in cytoprotection of the stomach and for the production of the pro-aggregatory prostanoid thromboxane by the platelets. In contrast, COX-2 is an inducible, immediate-early gene, and its role has been related to inflammation, reproduction and carcinogenesis. Expression of COX-2 is elevated in a variety of human malignancies and in their precursor lesions. Furthermore, genetic deletion or pharmacological inhibition of COX-2 suppresses tumour growth in several animal models of carcinogenesis. In humans, elevated COX-2 expression is associated with poor prognosis in adenocarcinomas of the digestive tract and the breast, and a selective inhibitor of COX-2 reduced polyp burden in patients who suffer from familial adenomatous polyposis. Thus, COX-2 seems to be a relevant target in chemoprevention.
Ristimäki
Ari
A
Department of Pathology, Helsinki University Central Hospital, Molecular and Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, Finland.
D000818:Animals; D002471:Cell Transformation, Neoplastic; D018890:Chemoprevention; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000473:pathology; D007527:Isoenzymes / Q000502:physiology*; D008565:Membrane Proteins; D009369:Neoplasms / Q000201:enzymology* / Q000517:prevention & control; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases