title: Characterization of cyclooxygenase-2 (COX-2) during tumorigenesis in human epithelial cancers: evidence for potential clinical utility of COX-2 inhibitors in epithelial cancers.
abstract: Increased prostaglandins (PGs) are associated with many inflammatory pathophysiological conditions; and are synthesized from arachidonic acid by either of 2 enzymes, cyclooxygenase-1 (COX-1) or -2 (COX-2). Recent epidemiologic, expression, and pharmacologic studies suggest COX-2 derived metabolites also play a functional role in the maintenance of tumor viability, growth and metastasis. Archival and/or prospectively collected human tissues were prepared for immunohistochemistry, and representative cases assayed via Western blot, RT-PCR, or TAQman analysis. Consistent overexpression of COX-2 was observed in a broad range of premalignant, malignant, and metastatic human epithelial cancers. COX-2 was detected in ca. 85% of the hyperproliferating, dysplastic, and neoplastic epithelial cells, and in the existing and angiogenic vasculature within and adjacent to hyperplastic/neoplastic lesions. These data collectively imply COX-2 may play an important role during premalignant hyperproliferation, as well as the later stages of invasive carcinoma and metastasis in various human epithelial cancers.
authors.affiliation: Pharmacia Corporation, 700 Chesterfield Pkway N, BB3K, St Louis, MO 63198, USA. Alane.T.Koki@pharmacia.com
authors.forename: A T
authors.initials: AT
authors.lastname: Koki
authors.forename: N K
authors.initials: NK
authors.lastname: Khan
authors.forename: B M
authors.initials: BM
authors.lastname: Woerner
authors.forename: K
authors.initials: K
authors.lastname: Seibert
authors.forename: J L
authors.initials: JL
authors.lastname: Harmon
authors.forename: A J
authors.initials: AJ
authors.lastname: Dannenberg
authors.forename: R A
authors.initials: RA
authors.lastname: Soslow
authors.forename: J L
authors.initials: JL
authors.lastname: Masferrer
mesh_terms: D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000201:enzymology* / Q000517:prevention & control; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases