title: 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.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, Okayama University Medical School, Okayama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Noguchi
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: I
authors.initials: I
authors.lastname: Yoshida
authors.forename: A
authors.initials: A
authors.lastname: Ashiba
authors.forename: J
authors.initials: J
authors.lastname: Tsuchiyama
authors.forename: K
authors.initials: K
authors.lastname: Shinagawa
authors.forename: T
authors.initials: T
authors.lastname: Yoshino
authors.forename: M
authors.initials: M
authors.lastname: Takata
authors.forename: M
authors.initials: M
authors.lastname: Harada
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D003598:Cytoskeletal Proteins; D017353:Gene Deletion; D015870:Gene Expression / Q000187:drug effects; D004854:Herpesvirus 4, Human; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000378:metabolism / Q000821:virology*; D060588:LIM Domain Proteins; D016399:Lymphoma, T-Cell / Q000378:metabolism / Q000821:virology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D016376:Oligonucleotides, Antisense; C484380:PDLIM7 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2