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Journal of Virology, January 2000, p. 883-891, Vol. 74, No. 2
Department of
Microbiology,1 Department of Radiation
Oncology,2 and Department of
Anatomy,3 The University of Hong Kong, Hong
Kong, People's Republic of China, and Cold Spring Harbor
Laboratory, Cold Spring Harbor, New York4
Received 26 July 1999/Accepted 7 October 1999
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 p16-insensitive CDK4R24C 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.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
LMP1 of Epstein-Barr Virus Induces Proliferation of
Primary Mouse Embryonic Fibroblasts and Cooperatively Transforms the
Cells with a p16-Insensitive CDK4 Oncogene
*
Corresponding author. Mailing address: Department of
Microbiology, The University of Hong Kong, Pathology Building, Queen Mary Hospital, Hong Kong, People's Republic of China. Phone:
852-2855-4892. Fax: 852-2855-1241. E-mail:
lcao{at}hkucc.hku.hk.
Journal of Virology, January 2000, p. 883-891, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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