1887

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Volume 77, Issue 8

Induction of apoptosis in epithelial cells by Epstein—Barr virus latent membrane protein 1 Free

Abstract

Epstein—Barr virus (EBV) induces human B cell transformation and is closely associated with naso-pharyngeal carcinoma. The expression of an EBV latent membrane protein, LMP-1, protects B cells from apoptosis by up-regulating the expression of a cellular oncogene, -2. LMP-1 also transforms rodent fibroblasts and affects the differentiation, morphology and growth of human and rodent epithelial cells. In this report, we describe a novel finding that high level expression of the LMP-1 gene in a human epithelial cell line (RHEK-1) induces apoptosis, characterized by chromosomal DNA fragmentation in the transfected cells. In particular, such an effect was more apparent under serum starvation. We also found that in the transfected RHEK-1 cells, LMP-1 expression neither affected -2 expression nor led the cells to grow in semisolid soft agar medium. These results indicate that LMP-1 may participate in the development of EBV-associated epithelial malignancy via a mechanism different from that seen in B cell or fibroblast transformation.

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© Journal of General Virology 1996
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1996-08-01
2023-12-05
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References

  1. Afanas’ev V. N., Korol’ B. A., Mantsygin Y. A., Nelipovich P. A., Pechatnikov V. A., Umansky S. R. 1986; Flow cytometry and biochemical analysis of DNA degradation characteristic of two types of cell death. FEBS Letters 194:347–350
     [Google Scholar]
  2. Arends M. J., Morris R. G., Wyllie A. H. 1990; Apoptosis: the role of the endonuclease. American Journal of Pathology 136:593–608
     [Google Scholar]
  3. Armentano D., Yu S. F., Kantoff P. W., von Ruden T., Anderson W. F., Gilboa E. 1987; Effect of internal viral sequences on the utility of retroviral vectors. Journal of Virology 61:1647–1650
     [Google Scholar]
  4. Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C., Seguin C., Tuffnell P. S., Barrell B. G. 1984; DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature 310:207–211
     [Google Scholar]
  5. Baichwal V. R., Sugden B. 1988; Transformation of Balb/3T3 cells by the BNLF-1 gene of Epstein—Barr virus. Oncogene 2:461–467
     [Google Scholar]
  6. Bankier A. T., Deininger P. L., Satchwell S. C., Baer R., Farrell P. J., Barrell B. G. 1983; DNA sequence analysis of the EcoRI Dhet fragment of B95-8 Epstein-Barr virus containing the terminal repeat sequences. Molecular Biology and Medicine 1:425–445
     [Google Scholar]
  7. Cleary M., Smith S., Sklar J. 1986; Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell 47:19–28
     [Google Scholar]
  8. Cory S. 1986; Activation of cellular oncogenes in hematopoietic cells by chromosome translocation. Advances in Cancer Research 47:189–234
     [Google Scholar]
  9. Dawson C. W., Rickinson A. B., Young L. S. 1990; Epstein-Barr virus latent membrane protein inhibits human epithelial cell differentiation. Nature 344:777–780
     [Google Scholar]
  10. Duvall E., Wyllie A. H. 1986; Death and the cell. Immunology Today 7:115–119
     [Google Scholar]
  11. Epstein M. A., Achong B. C., Barr Y. M. 1964; Vims particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet i:702–703
     [Google Scholar]
  12. Evan G. I., Wyllie A. H., Gilbert C. S., Littlewood T. D., Land H., Brooks M., Waters C. M., Penn L. Z., Hancock D. C. 1992; Induction of apoptosis in fibroblasts by c-Myc protein. Cell 69:119–128
     [Google Scholar]
  13. Fahraeus R., Fu J. L., Ernberg I., Finke I., Rowe M., Klein G., Falk K., Nilsson E., Yadav M., Busson P., Tursz T., Kallin B. 1988; Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma. International Journal of Cancer 42:329–338
     [Google Scholar]
  14. Fahraeus R., Rymo L., Rhim J. S., Klein G. 1990; Morphological transformation of human keratinocytes expressing the LMP-1 gene of Epstein-Barr vims. Nature 345:447–449
     [Google Scholar]
  15. Gregory C. D., Dive C., Henderson S., Smith C., Williams G. T., Gordon J., Rickinson A. B. 1991; Activation of Epstein-Barr vims latent genes protects human B cells from death by apoptosis. Nature 349:612–614
     [Google Scholar]
  16. Hammerschmidt W., Sugden B., Baichwal V. R. 1989; The transforming domain alone of the latent membrane protein of Epstein- Barr vims is toxic to cells when expressed at high levels. Journal of Virology 63:2469–2475
     [Google Scholar]
  17. Henderson S., Rowe M., Gregory C., Croom-Carter D., Wang F., Longnecker R., Kieff E., Rickinson A. B. 1991; Induction of bcl-2 expression by Epstein-Barr vims latent membrane protein 1 protects infected B cells from programmed cell death. Cell 65:1107–1115
     [Google Scholar]
  18. Henle G., Henie W. 1979; The vims as the etiologic agent of infectious mononucleosis. In The Epstein-Barr Virus pp 270–320 Edited by Epstein M. A., Achong B. G. Wien & Berlin: Springer-Verlag;
     [Google Scholar]
  19. Henle W., Henle G., Burtin P., Cachin Y., Clifford P., de Schryver A., de The G., Diehl V., Ho H. C., Klein G. 1970; Antibodies to Epstein-Barr vims in nasopharyngeal carcinoma, other head and neck neoplasms and control group. Journal of the National Cancer Institute 44:225–231
     [Google Scholar]
  20. Hennessy K., Fennewald S., Hummel M., Cole T., Kieff E. 1984; A membrane protein encoded by Epstein-Barr vims in latent growth transforming infection. Proceedings of the National Academy of Sciences, USA 81:7207–7211
     [Google Scholar]
  21. Hideaki H. I., Glenda C. G. 1993; Epstein-Barr vims infection is associated with increased apoptosis in untreated and phorbol ester- treated human Burkitt’s lymphoma (AW-Ramos) cells. Biochemical and Biophysical Research Communications 192:1415–1423
     [Google Scholar]
  22. Hu L. F., Chen F., Zheng X., Ernberg I., Cao S. L., Christensson B., Klein G., Winberg G. 1993; Clonability and tumorigenicity of human epithelial cells expressing the EBV encoded membrane protein LMP-1. Oncogene 8:1575–1583
     [Google Scholar]
  23. Hudson G. S., Farrell P. J., Barrell B. G. 1985; Two related but differentially expressed potential membrane proteins encoded by the EcoRI Dhet region of Epstein-Barr vims, B95.8. Journal of Virology 53:528–535
     [Google Scholar]
  24. Kawanishi M. 1993; Epstein-Barr vims induces fragmentation of chromosomal DNA during lytic infection. Journal of Virology 67:7654–7658
     [Google Scholar]
  25. Kerr J. F., Wyllie A. H., Currie A. R. 1972; Apoptosis: a biological phenomenon with wide-ranging implications in tissue kinetics. British Journal of Cancer 26:239–257
     [Google Scholar]
  26. Kieff E., Leibowitz D. 1990; Epstein-Barr vims and its replication. In Fields Virology, 2nd edn. pp 1889–1920 Edited by Fields B. N., Knipe D. M. New York: Raven Press;
     [Google Scholar]
  27. Liebowitz D., Wang D., Kieff E. 1986; Orientation and patching of the latent infection membrane protein encoded by Epstein-Barr vims. Journal of Virology 58:233–237
     [Google Scholar]
  28. Liebowitz D., Kopan R., Fuchs E., Sample J., Kieff E. 1987; An Epstein-Barr vims transforming protein associates with vimentin in lymphocytes. Molecular and Cellular Biology 7:2299–2308
     [Google Scholar]
  29. Lu Q. L., Elia G., Lucas S., Thomas A. 1993; Bcl-2 proto-oncogene expression in Epstein–Barr-virus-associated nasopharyngeal carcinoma. International Journal of Cancer 53:29–35
     [Google Scholar]
  30. McDonnell T. J., Deanee N., Platt F. M., Nunez G., Jaeger U., McKearn J. P., Korsmeyer S. J. 1989; bcl-2 immunoglobulin transgenic mice demonstrate extended B-cell survival and follicular lymphoproliferation. Cell 57:79–88
     [Google Scholar]
  31. Mann G. J., Dyne M., Musgrave E. A. 1987; Immuno fluorescence quantification of ribonucleotide reductase Ml subunit and correlation with DNA content by flow cytometry. Cytometry 8:509–517
     [Google Scholar]
  32. Mann K. P., Staunton D., Thorley-Lawson D. A. 1985; Epstein- Barr virus-encoded protein found in plasma membranes of transformed cells. Journal of Virology 55:710–720
     [Google Scholar]
  33. Niedobitek G., Fahraeus R., Herbst H., Latza U., Ferszt A., Klein G., Stein H. 1992; The Epstein-Barr vims encoded membrane protein (LMP) induces phenotypic changes in epithelial cells. Virchows Archiv B Cell Pathology 62:55–59
     [Google Scholar]
  34. Old L. J., Boyse E. A., Oettgen H. F., Deharven E., Geering G., Williamson B., Clifford P. 1966; Precipitating antibodies in human semm to an antigen present in cultured Burkitt’s lymphoma cells. Proceedings of the National Academy of Sciences, USA 56:1699–1704
     [Google Scholar]
  35. Rhim J. S., Jay G., Arnstein P., Price F. M., Sanford K. K., Aaronson S. A. 1985; Neoplastic transformation of human epidermal keratinocytes by Ad12–SV40 and Kirsten sarcoma vimses. Science 227:1250–1252
     [Google Scholar]
  36. Rowe M., Evans H. S., Young L. S., Hennessy K., Kieff E., Rickinson A. B. 1987; Monoclonal antibodies to the latent membrane protein of Epstein-Barr virus reveal heterogeneity of the protein and inducible expression in vims-transformed cells. Journal of General Virology 68:1575–1586
     [Google Scholar]
  37. Rowe M., Lear A. L., Croom-Carter D., Davies A. H., Rickinson A. B. 1992; Three pathways of Epstein-Barr vims gene activation from EBNAl-positive latency in B lymphocytes. Journal of Virology 66:122–131
     [Google Scholar]
  38. Rowe M., Peng-Pilon M., Huen D. S., Hardy R., Croom-Carter D., Lundgren E., Rickinson A. B. 1994; Upregulation of bcl-2 by the Epstein-Barr vims latent membrane protein 1: a B-cell-specific response that is delayed relative to NF-ĸ B activation and to induction of cell surface markers. Journal of Virology 68:5602–5612
     [Google Scholar]
  39. Spencer C. A., Groudine M. 1991; Control of c-myc regulation in normal and neoplastic cells. Advances in Cancer Research 56:1–48
     [Google Scholar]
  40. Telford W. G., King L. E., Fraker P. J. 1991; Evaluation of glucocorticoid-induced DNA fragmentation in mouse thymocytes by flow cytometry. Cell Proliferation 24:447–459
     [Google Scholar]
  41. Tsujimoto Y., Cossman J., Jaffe E., Croce M. 1985; Involvement of the bcl-2 gene in human follicular lymphoma. Science 228:1441–1443
     [Google Scholar]
  42. Wagner A. J., Small M. B., Hay N. 1993; Myc-mediated apoptosis is blocked by ectopic expression of bcl-2. Molecular and Cellular Biology 13:2432–2440
     [Google Scholar]
  43. Wang D., Liebowitz D., Kieff E. 1985; An EBV membrane protein expressed in immortalized lymphocytes transforms established rodent cells. Cell 43:831–840
     [Google Scholar]
  44. Wang D., Liebowitz D., Wang F., Gregory C., Rickinson A. B., Larson R., Springer T., Kieff E. 1988; Epstein-Barr virus latent infection membrane protein alters the human B-lymphocytes phenotype: deletion of the amino terminus abolishes activity. Journal of Virology 62:4173–4184
     [Google Scholar]
  45. White E. 1993; Regulation of apoptosis by the transforming genes of DNA tumor virus adenovirus. Proceedings of the Society for Experimental Biology and Medicine 204:30–39
     [Google Scholar]
  46. White E., Cipriani R., Sabbatini P., Dento A. 1991; The adenovirus ElB 19-kilodalton protein overcomes the cytotoxicity of E1A proteins. Journal of Virology 65:2968–2978
     [Google Scholar]
  47. Wilson J. B., Weinberg W., Johnson R., Yuspa S., Levine A. J. 1990; Expression of the BNLF-1 oncogene of Epstein–Barr virus in the skin of transgenic mice induces hyperplasia and aberrant expression of keratin 6. Cell 61:1315–1327
     [Google Scholar]
  48. Young L. S., Dawson C. W., Clark D., Rupani H., Busson P., Tursz T., Johnson A., Rickinson A. B. 1988; Epstein-Barr virus gene expression in nasopharyngeal carcinoma. Journal of General Virology 69:1051–1065
     [Google Scholar]
  49. Young L., Alfieri C., Hennessy K., Evans H., O’Hara C., Anderson K. C., Ritz J., Shapiro R. S., Rickinson A. B., Kieff E., Cohen J. I. 1989; Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease. New England Journal of Medicine 321:1080–1085
     [Google Scholar]
  50. Zheng X., Yuan F., Hu L., Chen F., Klein G., Christensson B. 1994; Effect of B-lymphocyte- and NPC-derived EBV-LMPl gene expression on in vitro growth and differentiation of human epithelial cells. International Journal of Cancer 57:747–753
     [Google Scholar]
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Induction of apoptosis in epithelial cells by Epstein—Barr virus latent membrane protein 1
J. Gen. Virol. 77, 1883 (1996); https://doi.org/10.1099/0022-1317-77-8-1883
/content/journal/jgv/10.1099/0022-1317-77-8-1883
/content/journal/jgv/10.1099/0022-1317-77-8-1883
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