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PMID: 17634231 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Epstein-Barr virus latent nuclear antigens can induce metastasis in a nude mouse model.

Journal of virology ·Vol. 81 ·No. 19 ·2007-10-00 ·Pages 10352-61

Kaul R, Murakami M, Choudhuri T, Robertson ES

Abstract

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus associated with the development of both lymphoid and epithelial tumors. The EBV critical latent antigens EBNA1 and EBNA3C interact with Nm23-H1, a known suppressor of cell migration and tumor metastasis. This interaction is critical for the regulation of downstream cellular genes involved in tumorigenesis and cell migration. The significance of these interactions was determined in nude mice using cancer cells expressing both EBV antigens and Nm23-H1. The EBV antigens promoted the growth of transformed cells in vivo, but their expression was less critical during the later stage of tumor development. The expression of Nm23-H1 affected the growth of cancer cells and suppressed their metastatic potential. This effect was effectively rescued by the expression of both EBV antigens. Interestingly, the prometastatic potential of EBNA3C was greater than that of EBNA1, which triggered a dramatic immune response, as indicated by increased spleen size and development of ascites in the mice. These studies now bridge the expression of the EBV antigens with tumorigenesis and metastasis and widen the range of potential targets for development of therapies for EBV-associated malignancies.

MeSH Terms
Animals Antigens, Viral/analysis,genetics,metabolism Cell Movement Cell Transformation, Neoplastic/genetics,metabolism Epstein-Barr Virus Nuclear Antigens/analysis,genetics,metabolism Humans Mice Mice, Nude Models, Animal NM23 Nucleoside Diphosphate Kinases Neoplasm Metastasis Neoplasms/chemistry,metabolism,pathology Nucleoside-Diphosphate Kinase/metabolism
Chemicals
Antigens, Viral EBNA-3C, epstein-barr virus Epstein-Barr Virus Nuclear Antigens NM23 Nucleoside Diphosphate Kinases NME1 protein, human Nme1 protein, mouse Nucleoside-Diphosphate Kinase EBV-encoded nuclear antigen 1
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kaul Rajeev
Department of Microbiology and Tumor Virology Program of the Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA.
Murakami Masanao
Choudhuri Tathagata
Robertson Erle S
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.00886-07
Published
2007-10-00
Epub
2007-00-18
Pages
10352-61
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC2045452
Subset
IM
Grants
NCI NIH HHS · R01 CA091792 · United States
NIDCR NIH HHS · DE014136 · United States
NIDCR NIH HHS · R01 DE014136 · United States
NCI NIH HHS · CA108461 · United States
NCI NIH HHS · CA091792 · United States
NCI NIH HHS · R01 CA108461 · United States
NCI NIH HHS · CA072510 · United States
External Links
PubMed source DOI: 10.1128/JVI.00886-07 PMC Full Text View journal details
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