title: Constitutive expression of the cyclooxygenase-2 gene in T-cell lines infected with human T cell leukemia virus type I.
abstract: Cyclooxygenase-2 (COX-2), an inducible enzyme that catalyzes the formation of prostaglandins and other eicosanoids from arachidonic acid, is constitutively expressed in several human carcinomas. COX-2 expression, however, has not been extensively studied in leukemia. Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia, an aggressive form of human T cell malignancy. We studied COX-2 mRNA expression in various human T-cell lines. Northern blot analysis revealed that COX-2 mRNA steady-state levels were high in 4 of 7 T-cell lines infected with HTLV-I. COX-2 mRNA, however, was not expressed in any of 3 HTLV-I-negative T-cell lines. We also confirmed COX-2 expression in 6 of 7 HTLV-I-positive T-cell lines by reverse transcription-PCR. HTLV-I Tax is known to increase the expression of cellular genes and thus we assayed Tax for its ability to increase transcription from the COX-2 promoter. Although Tax increased transcription of the COX-2 promoter in a T-cell line, Tax expression did not induce COX-2 mRNA expression, indicating that Tax alone is not sufficient for significant accumulation of COX-2 mRNA, which probably requires an additional viral protein. To evaluate the potential role of COX-2 in T cells, the HTLV-I-infected T-cell lines were treated with NS398, a selective COX-2 inhibitor. NS398 treatment inhibited proliferation and induced apoptosis of HTLV-I-infected T-cell lines and downregulated Bcl-2 and Bcl-x(L) mRNA expression, followed by chromosomal DNA fragmentation. Our data suggest that COX-2 is expressed selectively in T-cell lines infected with HTLV-I and that this gene may play a role in cell survival.
authors.affiliation: Department of Preventive Medicine and AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan. n-mori@net.nagasaki-u.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Mori
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Tanabe
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D016356:Gene Products, tax / Q000502:physiology; D019254:Genes, bcl-2; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000502:physiology; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000201:enzymology* / Q000821:virology; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; D016356:Gene Products, tax; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D013449:Sulfonamides; D051020:bcl-X Protein; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone