c-myc activation renders proliferation of Epstein-Barr virus (EBV)-transformed cells independent of EBV nuclear antigen 2 and latent membrane protein 1
| Autor: | Axel Polack, Alexander Pajic, Bettina Kempkes, Barbara Baier, C Geltinger, Josef Mautner, K. Hörtnagel, Georg W. Bornkamm, M. Falk, Barbara Christoph |
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| Jazyk: | angličtina |
| Rok vydání: | 1996 |
| Předmět: |
Gene Expression Regulation
Viral Herpesvirus 4 Human Recombinant Fusion Proteins Genes myc Biology medicine.disease_cause Transfection Proto-Oncogene Proteins c-myc Viral Matrix Proteins Antigen Antigens CD hemic and lymphatic diseases medicine Humans Cell Line Transformed Regulation of gene expression Multidisciplinary Expression vector Germinal center Immunoglobulin kappa locus Estrogens Flow Cytometry Epstein–Barr virus Molecular biology Burkitt Lymphoma Epstein-Barr Virus Nuclear Antigens Receptors Estrogen Cell culture Trans-Activators Cell Division Research Article |
| Popis: | Two genetic events contribute to the development of endemic Burkitt lymphoma (BL) infection of B lymphocytes with Epstein-Barr virus (EBV) and the activation of the protooncogene c-myc through chromosomal translocation. The viral genes EBV nuclear antigen 2 (EBNA2) and latent membrane protein 1 (LMP1) are essential for transformation of primary human B cells by EBV in vitro; however, these genes are not expressed in BL cells in vivo. To address the question whether c-myc activation might abrogate the requirement of the EBNA2 and LMP1 function, we have introduced an activated c-myc gene into an EBV-transformed cell line in which EBNA2 was rendered estrogen-dependent through fusion with the hormone binding domain of the estrogen receptor. The c-myc gene was placed under the control of regulatory elements of the immunoglobulin kappa locus composed a matrix attachment region, the intron enhancer, and the 3' enhancer. We show here that transfection of a c-myc expression plasmid followed by selection for high MYC expression is capable of inducing continuous proliferation of these cells in the absence of functional EBNA2 and LMP1. c-myc-induced hormone-independent proliferation was associated with a dramatic change in the growth behavior as well as cell surface marker expression of these cells. The typical lymphoblastoid morphology and phenotype of EBV-transformed cells completely changed into that of BL cells in vivo. We conclude that the phenotype of BL cells reflects the expression pattern of viral and cellular genes rather than its germinal center origin. |
| Databáze: | OpenAIRE |
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