Induction of apoptosis in epithelial cells by Epstein-Barr virus latent membrane protein 1.
Epstein-Barr virus (EBV) induces human B cell transformation and is closely associated with nasopharyngeal carcinoma. The expression of an EBV latent membrane protein, LMP-1, protects B cells from apoptosis by up-regulating the expression of a cellular oncogene, bcl-2. LMP-1 also transforms rodent fibroblasts and affects the differentiation, morphology and growth of human and rodent epithelial cells. In this report, we describe a novel finding that high level expression of the LMP-1 gene in a human epithelial cell line (RHEK-1) induces apoptosis, characterized by chromosomal DNA fragmentation in the transfected cells. In particular, such an effect was more apparent under serum starvation. We also found that in the transfected RHEK-1 cells, LMP-1 expression neither affected bcl-2 expression nor led the cells to grow in semisolid soft agar medium. These results indicate that LMP-1 may participate in the development of EBV-associated epithelial malignancy via a mechanism different from that seen in B cell or fibroblast transformation.
Lu
J J
JJ
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Chen
J Y
JY
Hsu
T Y
TY
Yu
W C
WC
Su
I J
IJ
Yang
C S
CS
D017209:Apoptosis; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D004847:Epithelial Cells; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D014162:Transfection; D014763:Viral Matrix Proteins / Q000235:genetics / Q000502:physiology*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014763:Viral Matrix Proteins