title: COX-2 gene polymorphisms and protein expression in renomedullary interstitial cell tumors.
abstract: Normal medullary interstitial cells regulate blood flow, water and salt absorption, and ultimately blood pressure through synthesis and secretion of prostanoids in which cycloxygenases play the rate-limiting steps. We found that most renomedullary interstitial cell tumors overexpressed cycloxygenase-2 (COX-2), with concomitant expression of microsomal prostaglandin E synthase-1 and the receptor for prostaglandin E2. Prostaglandin E2 is the major prostaglandin product of COX-2/microsomal prostaglandin E synthase-1 enzymatic pathway in medullary interstitial cells, and concomitant expression of COX-2, microsomal prostaglandin E synthase-1, and prostaglandin E2 receptor on interstitial cell tumors implies the presence of an autocrine growth loop important in pathogenesis of these tumors. Furthermore, overexpression of COX-2 protein was observed in association with homozygosity in several polymorphic sites within COX-2 gene (promoter region sites -1186 T/T and -765 G/G, intron 5 IVS5-275 T/T, and exon 10 Ex10+837 T>C), indicating their role in development of these tumors.
authors.affiliation: Department of Pathology, Creighton University Medical Center, Omaha, Nebraska 68131, USA. zorangatalica@creighton.edu
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gatalica
authors.forename: Stan L
authors.initials: SL
authors.lastname: Lilleberg
authors.forename: Manika Sapru
authors.initials: MS
authors.lastname: Koul
authors.forename: Tomas
authors.initials: T
authors.lastname: Vanecek
authors.forename: Ondrej
authors.initials: O
authors.lastname: Hes
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002999:Clone Cells; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000071876:Prostaglandin-E Synthases; D018078:Receptors, Prostaglandin E / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D018078:Receptors, Prostaglandin E; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases