Influence of Epstein-Barr virus latent gene expression on the apoptosis-inducing effects of cortisone and 2-chlorodeoxyadenosine (2-CDA) in B-cell lines.
Burkitt's lymphoma (BL) cell lines are heterogenous with regard to phenotype, growth characteristics, Epstein-Barr virus (EBV) latent gene and BCL-2 expression. Previously we have demonstrated that transfection with the EBV genes LMP or EBNA-2 upregulates BCL-2 in B-cell lines. In order to test the functional relevance of these findings, cell lines were examined with regard to their sensitivity towards different apoptosis-inducing agents. BL cell lines transfected with LMP expressed high levels of BCL-2, and were compared with the parental cell line expressing little or no BCL-2. We also studied EBV immortalized lymphoblastoid cell lines (LCL) with high BCL-2 expression and strong resistance towards low serum concentrations. Hydrocortisone (HC) and 2-chlorodeoxyadenosine (2-CDA) were used alone or in different combinations. Cell growth and apoptosis were studied morphologically and by determination of viability and DNA fragmentation. BL cell lines showed different sensitivity towards HC-induced apoptosis, and sensitive cell lines became more resistant towards HC after infection with EBV or transfection with LMP and subsequent upregulation of BCL-2 expression. BL cell lines and LCL were relatively insensitive towards 2-CDA-induced apoptosis, and high concentrations of 2-CDA were necessary, independently of the levels of BCL-2 expression. In contrast to low-grade non-Hodgkin's lymphomas, 2-CDA does not appear to be a valuable drug for the treatment of Burkitt's lymphoma. LMP expression provides resistance towards hydrocortisone-induced apoptosis in vitro, possible through upregulation of BCL-2.
Röth
A
A
Department of Hematology and Oncology, University of Freiburg Medical Center, Germany.
Pfaff
P
P
Lange
W
W
Finke
J
J
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001402:B-Lymphocytes; D002051:Burkitt Lymphoma; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002472:Cell Transformation, Viral; D017338:Cladribine / Q000494:pharmacology*; D003348:Cortisone / Q000494:pharmacology*; D053938:DNA Fragmentation; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000096:biosynthesis*
D000970:Antineoplastic Agents; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D009856:Oncogene Proteins, Viral; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins; D017338:Cladribine; D003348:Cortisone