scholarly journals Expression of bcl-2 in Burkitt's lymphoma cell lines: induction by latent Epstein-Barr virus genes

Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 459-469 ◽  
Author(s):  
J Finke ◽  
R Fritzen ◽  
P Ternes ◽  
P Trivedi ◽  
KJ Bross ◽  
...  
Keyword(s):  
Cell Lines ◽  
Epstein Barr Virus ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Nuclear Antigen ◽  
Full Spectrum ◽  
Group Iii ◽  
Barr Virus ◽  
Group I ◽  
Epstein Barr

Abstract The bcl-2 oncogene blocks programmed cell death (apoptosis). Epstein- Barr virus (EBV) can immortalize B lymphocytes into continuously growing lymphoblastoid cell lines (LCL) by the coordinate expression of at least 9 latent genes (EBV nuclear antigen [EBNA] 1–6, latent membrane protein [LMP], and terminal proteins [TP] 1 and 2). We analyzed transcription and expression of bcl-2 and latent EBV genes in Burkitt's lymphoma (BL) cell lines with a germinal center phenotype (group I) as well as activated BL cell lines (group III) and LCLs. We found high expression of bcl-2 as well as the full spectrum of latent EBV genes in LCLs and activated group III BL cell lines. Group I BL cells expressed little or no bcl-2, EBNA-2, and LMP. Superinfection with nondefective EBV or an EBNA-2-defective virus as well as transfection with EBNA-2- or LMP-carrying vectors into the EBV-negative cell lines RAMOS, DG75, U698, or BJAB induced upregulation of bcl-2 expression. The strongest effect on bcl-2 was obtained by transfection with LMP, or infection with the nondefective virus. No change of bcl-2 expression was observed with EBNA-1. Our data indicate that the immortalization capacity of EBV and the growth advantage of EBV- positive compared with EBV-negative BL cells in vitro may predominantly be mediated via induction of bcl-2 and the main effectors are EBNA-2 and LMP.

scholarly journals Expression of bcl-2 in Burkitt's lymphoma cell lines: induction by latent Epstein-Barr virus genes

Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 459-469 ◽  
Author(s):  
J Finke ◽  
R Fritzen ◽  
P Ternes ◽  
P Trivedi ◽  
KJ Bross ◽  
...  
Keyword(s):  
Cell Lines ◽  
Epstein Barr Virus ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Nuclear Antigen ◽  
Full Spectrum ◽  
Group Iii ◽  
Barr Virus ◽  
Group I ◽  
Epstein Barr

The bcl-2 oncogene blocks programmed cell death (apoptosis). Epstein- Barr virus (EBV) can immortalize B lymphocytes into continuously growing lymphoblastoid cell lines (LCL) by the coordinate expression of at least 9 latent genes (EBV nuclear antigen [EBNA] 1–6, latent membrane protein [LMP], and terminal proteins [TP] 1 and 2). We analyzed transcription and expression of bcl-2 and latent EBV genes in Burkitt's lymphoma (BL) cell lines with a germinal center phenotype (group I) as well as activated BL cell lines (group III) and LCLs. We found high expression of bcl-2 as well as the full spectrum of latent EBV genes in LCLs and activated group III BL cell lines. Group I BL cells expressed little or no bcl-2, EBNA-2, and LMP. Superinfection with nondefective EBV or an EBNA-2-defective virus as well as transfection with EBNA-2- or LMP-carrying vectors into the EBV-negative cell lines RAMOS, DG75, U698, or BJAB induced upregulation of bcl-2 expression. The strongest effect on bcl-2 was obtained by transfection with LMP, or infection with the nondefective virus. No change of bcl-2 expression was observed with EBNA-1. Our data indicate that the immortalization capacity of EBV and the growth advantage of EBV- positive compared with EBV-negative BL cells in vitro may predominantly be mediated via induction of bcl-2 and the main effectors are EBNA-2 and LMP.

The Epstein-Barr Virus Nuclear Antigen 2 (EBNA2), a Protein Required for B Lymphocyte Immortalization, Induces the Synthesis of Type I Interferon in Burkitts Lymphoma Cell Lines

1999 ◽  
Vol 380 (2) ◽  
Author(s):  
K. Kanda ◽  
B. Kempkes ◽  
G.W. Bornkamm ◽  
A. von Gabain ◽  
T. Decker
Keyword(s):  
Cell Lines ◽  
Epstein Barr Virus ◽  
Burkitt’S Lymphoma ◽  
Lymphoma Cell ◽  
Burkitt's Lymphoma ◽  
Nuclear Antigen ◽  
Type I ◽  
Barr Virus ◽  
Epstein Barr ◽  
Transcriptional Induction

AbstractEpstein-Barr virus nuclear antigen 2 (EBNA2), a protein involved in cell transformation, interferes with the cellular response to type I interferons (IFN-α/β). We investigated the function of conditionally expressed EBNA2 in the context of the IFN response in Burkitt's lymphoma cell lines. Expression of EBNA2 led to the transcriptional activation of both endogenous or transfected IFN-stimulated genes (ISGs), genes which contain within their promoters either the interferon-stimulated response element (ISRE) or the gamma interferon activation site (GAS). In search of a molecular mechanism for the transcriptional induction of ISGs, we observed an EBNA2-dependent synthesis of IFN-β mRNA at low levels and the secretion of low amounts of IFN. A transfected IFN-β promoter responded to EBNA2 activation, and a sequence closely resembling a RBP-Jκ binding site was pinpointed as a potential target of EBNA2 activity. EBNA2-dependent transcriptional induction of the IFN-β promoter occurred in EBV-negative Burkitt's lymphoma cells, indicating that other EBV genes were not required for the induction of IFN-β synthesis.

Modulation of Caspase-8 and FLICE-Inhibitory Protein Expression as a Potential Mechanism of Epstein-Barr Virus Tumorigenesis in Burkitt’s Lymphoma

Blood ◽  
1999 ◽  
Vol 94 (5) ◽  
pp. 1727-1737 ◽  
Author(s):  
Clifford G. Tepper ◽  
Michael F. Seldin
Keyword(s):  
Cell Lines ◽  
Epstein Barr Virus ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Pcr Analysis ◽  
Caspase 8 ◽  
Rt Pcr ◽  
Inhibitory Protein ◽  
Barr Virus ◽  
Epstein Barr

Abstract Ligation of the Fas receptor induces death-inducing signaling complex (DISC) formation, caspase activation, and subsequent apoptotic death of several cell types. Epstein-Barr virus (EBV)-positive group III Burkitt’s lymphoma (BL) cell lines have a marked resistance to Fas-mediated apoptosis, although expressing each of the DISC components, Fas/ APO-1–associated death domain protein (FADD), and caspase-8 (FLICE/MACH/Mch5). The apoptotic pathway distal to the DISC is intact because ceramide analogs, staurosporine, and granzyme B activate caspase-3 and induce apoptosis. Fas resistance was not explained by the putative death-attenuating caspase-8 isoforms. However, while Fas-activated cytosolic extracts from sensitive cells were capable of processing both procaspase-8 and procaspase-3 into active subunit forms, resistant cell extracts did not possess either of these activities. Accordingly, reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed higher transcript levels for the FLICE-inhibitory protein (FLIPL) in resistant cells and the ratio of caspase-8 to FLIPLmeasured by competition RT-PCR analysis directly correlated with susceptibility to Fas-mediated apoptosis of all cell lines. In addition, modification of the caspase-8/FLIPL ratio by caspase-8 or FLIPL overexpression was able to alter the susceptibility status of the cell lines tested. Our results imply that the relative levels of caspase-8 and FLIPL are an important determinant of susceptibility to Fas-mediated apoptosis.

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