This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ruf, I. K.
Right arrow Articles by Sample, J. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ruf, I. K.
Right arrow Articles by Sample, J. T.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 1999, p. 1651-1660, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Epstein-Barr Virus Regulates c-MYC, Apoptosis, and Tumorigenicity in Burkitt Lymphoma

Ingrid K. Ruf,1 Paul W. Rhyne,1 Hui Yang,2 Corina M. Borza,3 Lindsey M. Hutt-Fletcher,3 John L. Cleveland,2,4 and Jeffery T. Sample1,5,*

Program in Viral Oncogenesis and Tumor Immunology, Department of Virology and Molecular Biology,1 and Department of Biochemistry,2 St. Jude Children's Research Hospital, Memphis, Tennessee 38105; School of Biological Sciences, University of Missouri---Kansas City, Kansas City, Missouri 641103; and Department of Biochemistry4 and Department of Pathology,5 University of Tennessee Health Sciences Center, Memphis, Tennessee 38163

Received 11 June 1998/Returned for modification 16 July 1998/Accepted 30 November 1998

Loss of the Epstein-Barr virus (EBV) genome from Akata Burkitt lymphoma (BL) cells is coincident with a loss of malignant phenotype, despite the fact that Akata and other EBV-positive BL cells express a restricted set of EBV gene products (type I latency) that are not known to overtly affect cell growth. Here we demonstrate that reestablishment of type I latency in EBV-negative Akata cells restores tumorigenicity and that tumorigenic potential correlates with an increased resistance to apoptosis under growth-limiting conditions. The antiapoptotic effect of EBV was associated with a higher level of Bcl-2 expression and an EBV-dependent decrease in steady-state levels of c-MYC protein. Although the EBV EBNA-1 protein is expressed in all EBV-associated tumors and is reported to have oncogenic potential, enforced expression of EBNA-1 alone in EBV-negative Akata cells failed to restore tumorigenicity or EBV-dependent down-regulation of c-MYC. These data provide direct evidence that EBV contributes to the tumorigenic potential of Burkitt lymphoma and suggest a novel model whereby a restricted latency program of EBV promotes B-cell survival, and thus virus persistence within an immune host, by selectively targeting the expression of c-MYC.

* Corresponding author. Mailing address: Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105. Phone: (901) 495-3467. Fax: (901) 523-2622. E-mail: jeff.sample{at}stjude.org.

Molecular and Cellular Biology, March 1999, p. 1651-1660, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Houmani, J. L., Davis, C. I., Ruf, I. K. (2009). Growth-Promoting Properties of Epstein-Barr Virus EBER-1 RNA Correlate with Ribosomal Protein L22 Binding. J. Virol. 83: 9844-9853 [Abstract] [Full Text]  
  • Garrison, S. P., Jeffers, J. R., Yang, C., Nilsson, J. A., Hall, M. A., Rehg, J. E., Yue, W., Yu, J., Zhang, L., Onciu, M., Sample, J. T., Cleveland, J. L., Zambetti, G. P. (2008). Selection against PUMA Gene Expression in Myc-Driven B-Cell Lymphomagenesis. Mol. Cell. Biol. 28: 5391-5402 [Abstract] [Full Text]  
  • Kang, M.-S., Soni, V., Bronson, R., Kieff, E. (2008). Epstein-Barr Virus Nuclear Antigen 1 Does Not Cause Lymphoma in C57BL/6J Mice. J. Virol. 82: 4180-4183 [Abstract] [Full Text]  
  • Kelly, G. L., Rickinson, A. B. (2007). Burkitt Lymphoma: Revisiting the Pathogenesis of a Virus-Associated Malignancy. ASH Education Book 2007: 277-284 [Abstract] [Full Text]  
  • Kelly, G. L., Milner, A. E., Baldwin, G. S., Bell, A. I., Rickinson, A. B. (2006). Three restricted forms of Epstein-Barr virus latency counteracting apoptosis in c-myc-expressing Burkitt lymphoma cells. Proc. Natl. Acad. Sci. USA 103: 14935-14940 [Abstract] [Full Text]  
  • Ruf, I. K., Lackey, K. A., Warudkar, S., Sample, J. T. (2005). Protection from Interferon-Induced Apoptosis by Epstein-Barr Virus Small RNAs Is Not Mediated by Inhibition of PKR. J. Virol. 79: 14562-14569 [Abstract] [Full Text]  
  • Kelly, G. L., Milner, A. E., Tierney, R. J., Croom-Carter, D. S. G., Altmann, M., Hammerschmidt, W., Bell, A. I., Rickinson, A. B. (2005). Epstein-Barr Virus Nuclear Antigen 2 (EBNA2) Gene Deletion Is Consistently Linked with EBNA3A, -3B, and -3C Expression in Burkitt's Lymphoma Cells and with Increased Resistance to Apoptosis. J. Virol. 79: 10709-10717 [Abstract] [Full Text]  
  • Kang, M.-S., Lu, H., Yasui, T., Sharpe, A., Warren, H., Cahir-McFarland, E., Bronson, R., Hung, S. C., Kieff, E. (2005). Epstein-Barr virus nuclear antigen 1 does not induce lymphoma in transgenic FVB mice. Proc. Natl. Acad. Sci. USA 102: 820-825 [Abstract] [Full Text]  
  • Ricci, M. S., Jin, Z., Dews, M., Yu, D., Thomas-Tikhonenko, A., Dicker, D. T., El-Deiry, W. S. (2004). Direct Repression of FLIP Expression by c-myc Is a Major Determinant of TRAIL Sensitivity. Mol. Cell. Biol. 24: 8541-8555 [Abstract] [Full Text]  
  • Thompson, M. P., Kurzrock, R. (2004). Epstein-Barr Virus and Cancer. Clin. Cancer Res. 10: 803-821 [Abstract] [Full Text]  
  • Karajannis, M. A., Hummel, M., Oschlies, I., Anagnostopoulos, I., Zimmermann, M., Stein, H., Parwaresch, R., Reiter, A. (2003). Epstein-Barr virus infection in Western European pediatric non-Hodgkin lymphomas. Blood 102: 4244-4244 [Full Text]  
  • Kennedy, G., Komano, J., Sugden, B. (2003). Epstein-Barr virus provides a survival factor to Burkitt's lymphomas. Proc. Natl. Acad. Sci. USA 100: 14269-14274 [Abstract] [Full Text]  
  • Sheng, W., Decaussin, G., Ligout, A., Takada, K., Ooka, T. (2003). Malignant Transformation of Epstein-Barr Virus-Negative Akata Cells by Introduction of the BARF1 Gene Carried by Epstein-Barr Virus. J. Virol. 77: 3859-3865 [Abstract] [Full Text]  
  • Leoncini, L, Lazzi, S, Bellan, C, Tosi, P (2002). Cell kinetics and cell cycle regulation in lymphomas. J. Clin. Pathol. 55: 648-655 [Abstract] [Full Text]  
  • Maruo, S., Nanbo, A., Takada, K. (2001). Replacement of the Epstein-Barr Virus Plasmid with the EBER Plasmid in Burkitt's Lymphoma Cells. J. Virol. 75: 9977-9982 [Abstract] [Full Text]  
  • Trivedi, P., Spinsanti, P., Cuomo, L., Volpe, M., Takada, K., Frati, L., Faggioni, A. (2001). Differential Regulation of Epstein-Barr Virus (EBV) Latent Gene Expression in Burkitt Lymphoma Cells Infected with a Recombinant EBV Strain. J. Virol. 75: 4929-4935 [Abstract] [Full Text]  
  • Komano, J., Takada, K. (2001). Role of bcl-2 in Epstein-Barr Virus-Induced Malignant Conversion of Burkitt's Lymphoma Cell Line Akata. J. Virol. 75: 1561-1564 [Abstract] [Full Text]  
  • Swart, R., Ruf, I. K., Sample, J., Longnecker, R. (2000). Latent Membrane Protein 2A-Mediated Effects on the Phosphatidylinositol 3-Kinase/Akt Pathway. J. Virol. 74: 10838-10845 [Abstract] [Full Text]  
  • Hecht, J. L., Aster, J. C. (2000). Molecular Biology of Burkitt's Lymphoma. JCO 18: 3707-3721 [Abstract] [Full Text]  
  • Ruf, I. K., Rhyne, P. W., Yang, C., Cleveland, J. L., Sample, J. T. (2000). Epstein-Barr Virus Small RNAs Potentiate Tumorigenicity of Burkitt Lymphoma Cells Independently of an Effect on Apoptosis. J. Virol. 74: 10223-10228 [Abstract] [Full Text]  
  • Takada, K (2000). Epstein-Barr virus and gastric carcinoma. Mol. Pathol. 53: 255-261 [Abstract] [Full Text]  
  • Gregory, M. A., Hann, S. R. (2000). c-Myc Proteolysis by the Ubiquitin-Proteasome Pathway: Stabilization of c-Myc in Burkitt's Lymphoma Cells. Mol. Cell. Biol. 20: 2423-2435 [Abstract] [Full Text]  
  • Wade, M., Allday, M. J. (2000). Epstein-Barr Virus Suppresses a G2/M Checkpoint Activated by Genotoxins. Mol. Cell. Biol. 20: 1344-1360 [Abstract] [Full Text]  
  • Komano, J., Maruo, S., Kurozumi, K., Oda, T., Takada, K. (1999). Oncogenic Role of Epstein-Barr Virus-Encoded RNAs in Burkitt's Lymphoma Cell Line Akata. J. Virol. 73: 9827-9831 [Abstract] [Full Text]  
  • Ruf, I. K., Sample, J. (1999). Repression of Epstein-Barr Virus EBNA-1 Gene Transcription by pRb during Restricted Latency. J. Virol. 73: 7943-7951 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»