Involvement of 5-lipoxygenase in survival of Epstein-Barr virus (EBV)-converted B lymphoma cells

被引:19
作者
Belfiore, Maria Cristina
Natoni, Alessandro
Barzellotti, Roberta
Merendino, Nicolo'
Pessina, Gloria
Ghibelli, Lina
Gualandi, Giamplero
机构
[1] Univ Tuscia, DABAC, I-01100 Viterbo, Italy
[2] Univ Tuscia, DiSA, I-01100 Viterbo, Italy
[3] Univ Roma Tor Vergata, Dipartimento Biol, Rome, Italy
关键词
apoptosis; peroxides; LOXs; Epstein-Barr virus; lymphoma cells; quantitative RT-PCR;
D O I
10.1016/j.canlet.2007.03.010
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Epstein-Barr Virus (EBV) is involved in the progression of lymphomas through still unknown mechanism involving increased resistance to induced apoptosis. We show here that in a set of apoptosis-resistant EBV-converted Burkitt's lymphoma clones, 5- and 12-lipoxygenases (LOXs) are over-expressed. Further investigations on 5-LOX showed that resistance to apoptosis increases parallely with the expression of 5-lipoxygenase (5-LOX). Inhibitors of 5-LOX: (a) decrease peroxides level, indicating that this enzyme promotes the generation of oxidative stress in EBV+ cells, and (b) potently induce apoptosis in the EBV resistant cell line E2R. 5- and 15-HETE, the products of the 5 and 15-LOXs, respectively, counteract 5-LOX inhibitor induced apoptosis, indicating that products of arachidonate metabolism, rather than peroxides, trigger a signal transduction that is required for survival of the EBV-converted cells. These findings suggest that 5- and, to a lesser extent, other LOXs, that are involved in tumor progression of several cell types, may also participate in lymphomagenesis, especially that EBV-mediated. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:236 / 243
页数:8
相关论文
共 32 条
[1]   SEPARATION OF OXIDANT-INITIATED AND REDOX-REGULATED STEPS IN THE NF-KAPPA-B SIGNAL-TRANSDUCTION PATHWAY [J].
ANDERSON, MT ;
STAAL, FJT ;
GITLER, C ;
HERZENBERG, LA ;
HERZENBERG, LA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (24) :11527-11531
[2]  
Bonizzi G, 1999, MOL CELL BIOL, V19, P1950
[3]   Oxidative stress and nuclear factor-κB activation -: A reassessment of the evidence in the light of recent discoveries [J].
Bowie, A ;
O'Neill, LAJ .
BIOCHEMICAL PHARMACOLOGY, 2000, 59 (01) :13-23
[4]   Epstein-Barr virus latent membrane protein 1 (LMP1) activates the phosphatidylinositol 3-kinase/Akt pathway to promote cell survival and induce actin filament remodeling [J].
Dawson, CW ;
Tramountanis, G ;
Eliopoulos, AG ;
Young, LS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (06) :3694-3704
[5]   Multiple signal pathways are involved in the mitogenic effect of 5(S)-HETE in human pancreatic cancer [J].
Ding, XZ ;
Tong, WG ;
Adrian, TE .
ONCOLOGY, 2003, 65 (04) :285-294
[6]   P53 IS FREQUENTLY MUTATED IN BURKITTS-LYMPHOMA CELL-LINES [J].
FARRELL, PJ ;
ALLAN, GJ ;
SHANAHAN, F ;
VOUSDEN, KH ;
CROOK, T .
EMBO JOURNAL, 1991, 10 (10) :2879-2887
[7]   Inducible loss of NF-κB activity is associated with apoptosis and Bcl-2 down-regulation in Epstein-Barr virus-transformed B lymphocytes [J].
Feuillard, J ;
Schuhmacher, M ;
Kohanna, S ;
Asso-Bonnet, M ;
Ledeur, F ;
Joubert-Caron, R ;
Bissières, P ;
Polack, A ;
Bornkamm, GW ;
Raphaël, M .
BLOOD, 2000, 95 (06) :2068-2075
[8]   5-LIPOXYGENASE [J].
FORDHUTCHINSON, AW ;
GRESSER, M ;
YOUNG, RN .
ANNUAL REVIEW OF BIOCHEMISTRY, 1994, 63 :383-417
[9]  
GARGANO S, 1992, CANCER, V4, P205
[10]   Protease inhibitors block apoptosis at intermediate stages: A compared analysis of DNA fragmentation and apoptotic nuclear morphology [J].
Ghibelli, L ;
Maresca, V ;
Coppola, S ;
Gualandi, G .
FEBS LETTERS, 1995, 377 (01) :9-14