MDM2 expression in EBV-infected nasopharyngeal carcinoma cells
Journal
Laboratory Investigation
Journal Volume
84
Journal Issue
12
Pages
1547-1556
Date Issued
2004
Author(s)
Abstract
To understand whether the p53-regulated mdm2 gene expression was altered by the Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC), the NPC-TW01 cell line was infected EBV through IgA receptor-mediated endocytosis. The mdm2 gene was expressed only in a small fraction of the NPC cell population and could be enhanced in the EBV-infected (EBV+) cells. In the animals bearing EBV+ and EBV- NPC xenografts, the MDM2+ cells only appeared in clusters in both EBV+ and EBV- tumors with stronger expression in EBV+ cells. Cotransfection of pmdm2-Luc plus pSV40-p53 plus pCMV-LMP1 in the NPC-TW06 line that had p53 heterozygous point mutation showed stronger mdm2 promoter activity than cells cotransfected with pmdm2-Luc plus pSV40-p53, but no mdm2 promoter activity was seen in cells cotransfected with pmdm2-Luc plus pCMV-LMP1. Only the EBV-LMP1 but not the EBV-LMP24 gene could enhance p53 to upregulated mdm2 expression. Tumor cells in NPC biopsy specimens revealed similar mdm2 expression as in the animal model. It is concluded that although EBV can indirectly enhance mdm2 gene expression in tumor cells that express this gene, it cannot turn on or directly regulate mdm2 expression in cells that do not express this gene. In other words, EBV plays a role as an enhancer in NPC tumorigenesis.
Subjects
Cotransfection of pmdm2-Luc; EBV infection; LMP1; mdm2 expression; Nasopharyngeal carcinoma; psv40-p53
SDGs
Other Subjects
immunoglobulin receptor; protein MDM2; article; cancer cell culture; carcinogenesis; cell population; controlled study; endocytosis; Epstein Barr virus; gene expression; genetic transfection; human; human cell; nasopharynx carcinoma; nonhuman; point mutation; priority journal; promoter region; protein expression; tumor biopsy; tumor cell; upregulation; virus infection; xenograft; Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Endocytosis; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Viral; Herpesvirus 4, Human; Mice; Mice, SCID; Nasopharyngeal Neoplasms; Nuclear Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-mdm2; Transplantation, Heterologous; Zinc Fingers
Type
journal article