Involvement of 5-lipoxygenase in survival of Epstein-Barr virus (EBV)-converted B lymphoma cells.
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.
Belfiore
Maria Cristina
MC
DABAC, Universitá della Tuscia, Via SC de Lellis, 01100 Viterbo, Italy.
Natoni
Alessandro
A
Barzellotti
Roberta
R
Merendino
Nicolo'
N
Pessina
Gloria
G
Ghibelli
Lina
L
Gualandi
Giampiero
G
D017209:Apoptosis; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics* / Q000378:metabolism*; D002051:Burkitt Lymphoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000821:virology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D018450:Disease Progression; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D015227:Lipid Peroxidation; D012334:RNA, Neoplasm / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012334:RNA, Neoplasm; D017382:Reactive Oxygen Species; D001092:Arachidonate 12-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase