Antisense oligodeoxynucleotides to latent membrane protein 1 induce growth inhibition, apoptosis and Bcl‐2 suppression in Epstein‐Barr virus (EBV)‐transformed B‐lymphoblastoid cells, but not in EBV‐positive natural killer cell lymphoma cells

• Published in: British journal of haematology 2001-07, Vol.114 (1), p.84-92
• Main Authors: Noguchi, Toshio, Ikeda, Kazuma, Yamamoto, Kazuhiko, Yoshida, Isao, Ashiba, Atsuko, Tsuchiyama, Junjiro, Shinagawa, Katsuji, Yoshino, Tadashi, Takata, Minoru, Harada, Mine
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; antisense oligodeoxynucleotides; apoptosis; Apoptosis - drug effects; Biological and medical sciences; Blotting, Western; Carrier Proteins - genetics; Cell Division - drug effects; Cell Line, Transformed; Cytoskeletal Proteins; EBV‐positive NK‐cell lymphoma; Gene Deletion; Gene Expression - drug effects; Hematologic and hematopoietic diseases; Herpesvirus 4, Human; Humans; Intracellular Signaling Peptides and Proteins; Killer Cells, Natural - metabolism; Killer Cells, Natural - virology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; LIM Domain Proteins; LMP‐1; Lymphoma, T-Cell - metabolism; Lymphoma, T-Cell - virology; Medical sciences; Oligonucleotides, Antisense - pharmacology; proliferation; Proto-Oncogene Proteins c-bcl-2 - genetics; Reverse Transcriptase Polymerase Chain Reaction; Tumor Cells, Cultured
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2001.02887.x

Epstein‐Barr virus (EBV)‐encoded latent membrane protein 1 (LMP‐1) is essential for immortalization of B cells by EBV, protects the infected cells from apoptotic cell death and induces Bcl‐2 expression. Suppression of LMP‐1 expression by antisense oligodeoxynucleotides (AS‐oligo) to LMP‐1 inhibits proliferation, promotes apoptosis and suppresses Bcl‐2 expression in EBV‐transformed B cells. However, the function of LMP‐1 expression in EBV‐positive natural killer (NK) cell lymphoma cells has not been reported previously. We examined the function of LMP‐1 in two EBV‐positive NK cell lymphoma cell lines (NK‐YS and YT) through suppressing LMP‐1 expression by AS‐oligo to LMP‐1. The AS‐oligo to LMP‐1 suppressed LMP‐1 mRNA and protein expression in two EBV‐positive NK cell lymphoma cell lines, as well as in an EBV‐transformed B‐cell line (CMG‐1). Proliferation was inhibited, apoptosis was induced and Bcl‐2 expression was suppressed in CMG‐1 cells, but none of these events were observed in NK‐YS or YT cells. These results suggest that proliferation, inhibition of apoptosis and Bcl‐2 expression in EBV‐positive NK cell lymphoma cells are not directly regulated by LMP‐1 as in EBV‐transformed B‐cell lines, but are probably mediated through other signal transducing systems.