Tumor formation in nude mice inoculated with cultured human epithelial cells co-expressing Epstein-Barr virus latent membrane protein 1 and Bcl-2.
OBJECTIVE
To examine the tumor-forming in nude mice of human epithelial cells co-expressed Bcl-2 and EBV LMP-1 ability, the phenotype of tumor cells and their expression of oncogenes and tumor-suppressor genes.


METHODS
Following an in vivo tumorigenesis test in nude mice, the phenotype and growth properties of tumor cells were observed. Levels of expression of Bcl-2, and EBV LMP-1, and of onco- and tumor-suppressor proteins were detected by Western blot assay.


RESULTS
Human epithelial cells co-expressing Bcl-2 and EBV LMP-1 can form tumors in nude mice. Tumors appeared 48-65 days postinoculation in 6 of 10 nude mice tested but not in mice given Bcl-2-positive (0/5), LMP-1-positive (0/5) and RHEK-1 control (0/5) cells. Levels of c-myc protein were upregulated by LMP-1 but were not affected by Bcl-2 in this cell background; screening for other cellular oncogene and tumor suppressor gene products showed no change.


CONCLUSIONS
The complementary effects of EBV LMP-1 and Bcl-2 in human epithelial cells resulted in tumor formation in nude mice but did not affect the expression of onco- and tumor suppressor proteins except for elevated c-myc. These findings suggest that LMP-1 and Bcl-2 can contribute together to the formation of EBV-associated epithelial cell tumors.
Lu
John Jenn-Yenn
JJ
National Taichung Nursing College, Taichung, Taiwan, ROC. johnlu@ntcnc.edu.tw
Lay
Jong-Ding
JD
D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D020031:Epstein-Barr Virus Infections / Q000503:physiopathology / Q000821:virology; D019254:Genes, bcl-2; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D014412:Tumor Virus Infections; D014763:Viral Matrix Proteins / Q000378:metabolism*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019253:Proto-Oncogene Proteins c-bcl-2; D014763:Viral Matrix Proteins