LMP1 of Epstein-Barr virus induces proliferation of primary mouse embryonic fibroblasts and cooperatively transforms the cells with a p16-insensitive CDK4 oncogene

Yang, X. H., Sham, J. S. T., Ng, M. H., Tsao, S. W., Zhang, D. K., Lowe, S. W., Cao, L. (January 2000) LMP1 of Epstein-Barr virus induces proliferation of primary mouse embryonic fibroblasts and cooperatively transforms the cells with a p16-insensitive CDK4 oncogene. Journal of Virology, 74 (2). pp. 883-891. ISSN 0022-538X

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URL: http://www.ncbi.nlm.nih.gov/pubmed/10623751
DOI: 10.1128/JVI.74.2.883-891.2000

Abstract

The latent membrane protein LMP1 of Epstein-Barr virus (EBV) is often present in EBV-associated malignancies including nasopharyngeal carcinoma and Hodgkin's lymphoma. Previous work demonstrates that the LMP1 gene of EBV is sufficient to transform certain established rodent fibroblast cell lines and to induce the tumorigenicity of some human epithelial cell lines. In addition, LMP1 plays pleiotropic roles in cell growth arrest, differentiation, and apoptosis, depending on the background of the target cells. To examine the roles of LMP1 in cell proliferation and growth regulation in primary culture cells, we constructed a recombinant retrovirus containing an LMP1 gene. With this retrovirus, LMP1 was shown to stimulate the proliferation of primary mouse embryonic fibroblasts (MEF cells). It has a mitogenic activity for MEF cells, as demonstrated by an immediate induction of cell doubling time, In addition, it significantly extends the passage number of MEF cells to more than 30 after retroviral infection, compared with less than 5 for uninfected MEF cells. Furthermore, LMP1 cooperates with a pl6-insensitive CDK4(R24C) oncogene in transforming MEF cells. Our results provide the first evidence of the abilities of the LMP1 gene, acting alone, to effectively induce the proliferation of primary MEF cells and of its cooperativity with another cellular oncogene in transforming primary cells.

Item Type: Paper
Uncontrolled Keywords: LATENT MEMBRANE-PROTEIN LYMPHOCYTE GROWTH TRANSFORMATION NF-KAPPA-B HUMAN EPITHELIAL-CELLS EXPRESSION P53 MEMBRANE-PROTEIN-1 ACTIVATION APOPTOSIS INDUCTION
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
organism description > virus
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: Matt Covey
Date: January 2000
Date Deposited: 30 Jan 2014 20:03
Last Modified: 30 Jan 2014 20:03
PMCID: PMC111609
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29411

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