Alterations of biologic properties and gene expression in nasopharyngeal epithelial cells by the Epstein-Barr virus-encoded latent membrane protein 1.
Undifferentiated nasopharyngeal carcinoma (NPC) is closely associated with EBV infection, and the EBV-encoded latent membrane protein 1 (LMP1) is frequently detected in NPC. However, little is known about the pathologic roles of LMP1 in this disease. Recently, we reported the morphologic transformation and increased expression of the LAMC2 and ITGalpha6 genes in LMP1-expressing NPC cell lines. In this study, we further examine the effects of LMP1 in an immortalized nasopharyngeal epithelial cell line called NP69. This cell line was established from primary nonmalignant nasopharyngeal epithelial cells and may represent a model of premalignant nasopharyngeal epithelial cells. LMP1 induced many phenotypic changes in NP69 cells. These include morphologic transformation, increased cell proliferation, anchorage-independent growth, resistance to serum free-induced cell death, and enhanced cell migration and invasion. In addition, expression array analysis identified 28 genes that demonstrated a more than 2-fold difference in expression of NP69 cells expressing LMP1 when compared with a vector control. Two of the up-regulated genes (VEGF and vimentin) identified have been previously reported as LMP1 targets. The majority of the identified genes are associated with cell growth, differentiation, cell shape, and invasion. The present findings support the proposed roles of LMP1 in promoting cell transformation, migration, and invasion in premalignant nasopharyngeal epithelial cells. The present study also indicates the activation of the Ras/MAPK pathway in LMP1-expressing cells, which may be involved in mediating some of the transforming effects of LMP1 observed in nasopharyngeal epithelial cells.
Lo
Angela Kwok Fung
AK
Department of Anatomy, The University of Hong Kong, Hong Kong SAR, China.
Liu
Yu
Y
Wang
Xiang Hong
XH
Huang
Dolly P
DP
Yuen
Po Wing
PW
Wong
Yong Chuan
YC
Tsao
George Sai Wah
GS
D015153:Blotting, Western; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D002470:Cell Survival; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000209:etiology*; D009305:Nasopharynx / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D014763:Viral Matrix Proteins / Q000502:physiology*; D018631:ras Proteins / Q000378:metabolism
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins