title: Induction of retinoic acid receptor-beta suppresses cyclooxygenase-2 expression in esophageal cancer cells.
abstract: Since retinoic acid receptor (RAR)-beta mRNA is frequently lost during esophageal carcinogenesis and esophageal cancer cells that do not express RAR-beta are resistant to retinoic acid (RA), we stably transfected RAR-beta expression vector into an esophageal cancer cell line TE-8 and an antisense RAR-beta into TE-3 cells. Transfection of RAR-beta decreased cell growth and colony formation and induced apoptosis in TE-8 cells. Antisense RAR-beta-transfected TE-3 cells had a shorter doubling time and became resistant to RA. Induction of RAR-beta decreased COX-2 expression in RAR-beta transfected TE-8 cells, whereas antisense RAR-beta transfected TE-3 cells increased COX-2 expression. The inhibitory effect of RAR-beta on COX-2 expression was further enhanced in the presence of RA, which was blocked by an RAR antagonist. The synthetic retinoid N-(4-hydroxyphenyl)retinamide, which does not bind effectively to RAR-beta, had no effect on COX-2 suppression. Furthermore, RA blocked bile acid-induced COX-2 expression and prostaglandin E(2) production only in the RAR-beta positive cells. Our data demonstrated that anticancer effect of RAR-beta may be related to its ability to suppress COX-2 expression and support that the loss of RAR-beta expression may contribute to esophageal carcinogenesis.
authors.affiliation: Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, TX 77030, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Shumei
authors.initials: S
authors.lastname: Song
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Xiao-kun
authors.initials: XK
authors.lastname: Zhang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
authors.forename: Reuben
authors.initials: R
authors.lastname: Lotan
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Xu
mesh_terms: D017209:Apoptosis; D001647:Bile Acids and Salts / Q000494:pharmacology; D015153:Blotting, Western; D002455:Cell Division; D002470:Cell Survival; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D016373:DNA, Antisense / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D001647:Bile Acids and Salts; D016373:DNA, Antisense; D007527:Isoenzymes; D008565:Membrane Proteins; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D014212:Tretinoin; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone