Cooperative interaction between Bcl-2 and Epstein-Barr virus latent membrane protein 1 in the growth transformation of human epithelial cells.
The Epstein-Barr virus latent membrane protein 1 (LMP-1) is essential for virus-induced B cell immortalization and can protect B lymphoma cell lines from apoptosis signals in vitro via induction of cellular Bcl-2 expression. However, we have reported that high-level expression of LMP-1 in epithelial cells (RHEK-1 cells) itself induces apoptosis. This apoptotic event occurs in the absence of detectable Bcl-2 expression in the LMP-1-transfected epithelial cells. In this study, we transfected the bcl-2 gene into the LMP-1-containing cells and examined the effect of Bcl-2 upon LMP-1-mediated apoptosis, and upon the growth phenotype of the transfected cells. The results show that ectopic expression of Bcl-2 specifically blocks apoptotic death induced by LMP-1. This was observed from cell culture viability and from gel electrophoresis and flow cytometric assays of the degree of DNA fragmentation in cultured cells. Furthermore, co-expression of LMP-1 and Bcl-2 in RHEK-1 cells enabled the cells to grow under low-serum conditions and to form colonies in semi-soft agar medium. These results suggest, therefore, that these two proteins play important complementary roles in the process of EBV-associated epithelial cell transformation. It appears significant, therefore, that LMP-1 and Bcl-2 are frequently co-expressed in the malignant cells of an EBV-positive epithelial tumour, nasopharyngeal carcinoma.
Lu
J J
JJ
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, ROC.
Chen
J Y
JY
Hsu
T Y
TY
Yu
W C
WC
Su
I J
IJ
Yang
C S
CS
D002455:Cell Division; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019253:Proto-Oncogene Proteins c-bcl-2; D014763:Viral Matrix Proteins