Expression of Epstein-Barr virus latent membrane protein 1 protects Jurkat T cells from apoptosis induced by serum deprivation.
It has been generally accepted that inhibition of apoptosis is important in the development of malignancy. To determine whether Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1), the virus-coded transforming oncogene product, has an anti-apoptotic function in non-B-cells, Jurkat T cells were transfected with the LMP1-expression vector pSV2gptMTLM consisting of the human metallothionein promoter and were selected for mycophonolic acid resistance. LMP1-expressing clones of Jurkat cells showed resistance to apoptosis induced by serum deprivation. In LMP1-expressing clones, although the levels of Bcl-2 and Bax were similar to those in the clones of vector transfectants or parental cells, c-Myc expression was significantly depressed. Down-regulation of c-Myc by LMP1 was confirmed by using LMP1-expressing clones treated with CdCl2. Addition of c-myc antisense oligonucleotides to Jurkat cells specifically inhibited apoptosis induced by serum deprivation at the concentrations which suppressed c-Myc expression. These results suggest that LMP1 expression and subsequent down-regulation of c-Myc protect Jurkat T cells from apoptosis induced by serum deprivation. The significance of the anti-apoptotic function of LMP1 in non-B, Jurkat T cells is discussed in relation to the pathogenesis of EBV malignancy.
Kawanishi
M
M
Department of Microbiology, Graduate School of Medicine, Kyoto University, Japan.
D017209:Apoptosis; D001769:Blood; D015967:Gene Expression Regulation, Viral; D019254:Genes, bcl-2; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D013601:T-Lymphocytes / Q000821:virology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000235:genetics / Q000502:physiology*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016271:Proto-Oncogene Proteins c-myc; D014763:Viral Matrix Proteins