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

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.

journal_name

Oncogene

journal_title

Oncogene

authors

Gao Y,Lu YJ,Xue SA,Chen H,Wedderburn N,Griffin BE

doi

10.1038/sj.onc.1205130

subject

Has Abstract

pub_date

2002-01-24 00:00:00

pages

825-35

issue

5

eissn

0950-9232

issn

1476-5594

journal_volume

21

pub_type

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