Epstein-Barr virus LMP1 modulates the malignant potential of gastric carcinoma cells involving apoptosis

Lai Fa Sheu, Ann Chen, Yu Hui Wei, Kuo Chieh Ho, Jye Young Cheng, Ching Liang Meng, Wei Hwa Lee

Research output: Contribution to journalArticle

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Abstract

About 10% of gastric carcinomas including lymphoepithelioma-like carcinoma and adenocarcinoma are associated with Epstein-Barr virus (EBV) infection. In EBV-associated gastric carcinomas, the tumor cells express Epstein-Barr nuclear antigen 1 (EBNA-1) but not EBNA-2, -3A, -3B, or -3C, leader protein, or latent membrane proteins (IMPs) because of gene methylation. Only a few exceptional cases have LMP1 expression in tumor cells as demonstrated by immunohistochemical studies. To elucidate the biological effects of LMP1 and the significance of its restricted expression in EBV- associated gastric carcinomas, the LMP1 gene was transferred into EBV- negative gastric carcinoma cell lines (SCM1 and TMC1) and into EBV-negative nasopharyngeal carcinoma (NPC) cells (HONE-1) as a control. The biological effects of LMP1 in gastric carcinoma cells were monitored in vitro and in vivo. These results showed that the consequence of LMP1 expression is a growth enhancement in NPC cells, but it is a growth suppression in gastric carcinoma cells. The LMP1-expressing gastric carcinoma cells had a reduced growth rate, colony-forming efficiency, mean colony size, and tumorigenicity and a lower malignant cytological grade. The reduced growth rate, colony- forming efficiency, and mean colony size were partially reversible in vitro with treatment with LMP1 antisense oligonucleotide. In addition, enhanced apoptosis was found in the LMP1-expressing gastric carcinoma cells. This suggests that LMP1 may negatively modulate the malignant potential of gastric carcinoma cells via an enhancement of apoptosis. We concluded that the restriction of LMP1 expression in EBV-associated gastric carcinomas may lead to a growth advantage for tumor cells by avoiding LMP1 apoptotic effects and immunologically mediated elimination.

Original languageEnglish
Pages (from-to)63-74
Number of pages12
JournalAmerican Journal of Pathology
Volume152
Issue number1
Publication statusPublished - Jan 1998
Externally publishedYes

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Human Herpesvirus 4
Stomach
Apoptosis
Carcinoma
Growth
Inosine Monophosphate
Neoplasms
Nuclear Antigens
Epstein-Barr Virus Infections
Antisense Oligonucleotides
Methylation
Genes
Membrane Proteins
Adenocarcinoma
Cell Line

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Sheu, L. F., Chen, A., Wei, Y. H., Ho, K. C., Cheng, J. Y., Meng, C. L., & Lee, W. H. (1998). Epstein-Barr virus LMP1 modulates the malignant potential of gastric carcinoma cells involving apoptosis. American Journal of Pathology, 152(1), 63-74.

Epstein-Barr virus LMP1 modulates the malignant potential of gastric carcinoma cells involving apoptosis. / Sheu, Lai Fa; Chen, Ann; Wei, Yu Hui; Ho, Kuo Chieh; Cheng, Jye Young; Meng, Ching Liang; Lee, Wei Hwa.

In: American Journal of Pathology, Vol. 152, No. 1, 01.1998, p. 63-74.

Research output: Contribution to journalArticle

Sheu, Lai Fa ; Chen, Ann ; Wei, Yu Hui ; Ho, Kuo Chieh ; Cheng, Jye Young ; Meng, Ching Liang ; Lee, Wei Hwa. / Epstein-Barr virus LMP1 modulates the malignant potential of gastric carcinoma cells involving apoptosis. In: American Journal of Pathology. 1998 ; Vol. 152, No. 1. pp. 63-74.
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