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Hypothesis: a novel route for immortalization of epithelial cells by Epstein-Barr virus

Oncogene volume 21, pages 825–835 (2002)Cite this article

Abstract

Transfection of primate tissue explants with a specific sub-fragment (p31) of EBV DNA results in epithelial (but no other) cells proliferating indefinitely (becoming ‘immortalized’) without evidence of a ‘growth crisis’. Molecular evidence supports integration of viral information into the host chromosome, and an early genotypic alteration involving specific amplification of a sub-component (IR1) of p31 DNA, followed by apparent loss of viral DNA from chromosomes, consistent with a ‘hit and run’ mechanism. However, analysis at the individual cell level during long-term culture, by FISH techniques, reveals chromosomal alterations, and viral sequences surviving within double minute (DM) bodies. Changing growth patterns occurring at different stages during propagation (>a year in culture) may be explained by sporadic reintegration of surviving viral DNA into the host chromosome. Notably, throughout culture, telomere lengths in chromosomal DNAs do not alter but rather retain the length observed in the primary cell populations. Introduction of a growth stimulating function of EBV, BARF1, into the immortalized, non-clonable epithelial cells under conditions which permit overexpression, allows clonal populations to be derived. Based on the data, mechanisms of immortalization, in the absence of a proven viral oncogene in p31 DNA, and possible genes involved, are considered.

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Acknowledgements

We thank the Cancer Research Campaign, UK and The Royal College of Surgeons of England for partial support of this work. S-A Xue gratefully acknowledges grant support from the European Community, contract no. IC18CT96-0132, and BE Griffin thanks the Leverhulme Foundation for an award.

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Author notes

  1. Yanning Gao

    Present address: Department of Etiology and Chemical Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences (CAMS), P.O. Box 2258, Beijing, 100021, PR, China

  2. Honglin Chen

    Present address: Molecular Virology Laboratories, Johns Hopkins School of Medicine, Baltimore, 21205-2185, Maryland, MD, USA

Authors and Affiliations

  1. Department of Medicine, Viral Oncology Unit, Imperial College of Science, Technology and Medicine, Norfolk Place, London, W2 1PG, UK

    Yanning Gao, Shao-An Xue, Nina Wedderburn & Beverly E Griffin

  2. Molecular Cytogenetics, Section of Cell Biology and Experimental Pathology, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK

    Yong-Jie Lu

  3. Department of Microbiology, University of Hong Kong, Queen Mary Hospital, Hong Kong, PR, China

    Honglin Chen

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Correspondence to Beverly E Griffin.

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Gao, Y., Lu, YJ., Xue, SA. et al. Hypothesis: a novel route for immortalization of epithelial cells by Epstein-Barr virus. Oncogene 21, 825–835 (2002). https://doi.org/10.1038/sj.onc.1205130

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