Latent membrane protein-1 of Epstein-Barr virus inhibits cell growth and induces sensitivity to cisplatin in nasopharyngeal carcinoma cells.
Nasopharyngeal carcinoma is closely associated with Epstein-Barr virus (EBV) and the EBV encoded latent membrane protein-1 expression (LMP1) is commonly found in the tumour cells. LMP1 has been shown to be involved in modulation of cell growth in B cells but the biological properties of LMP1 expression in nasopharyngeal carcinoma cells are less defined. In this study, a full length LMP1 gene was introduced into an EBV negative nasopharyngeal carcinoma cell line, CNE2, and five LMP1-expressing clones were isolated. Expression of LMP1 did not confer cell growth advantage in CNE2 cells; instead, it induced growth inhibition both in vitro and in vivo. In addition, the LMP1 transfected cells were more susceptible to cisplatin-induced cell death and showed 1.4-4.0-fold increased sensitivity to cisplatin compared to the vector infected control clones. The effect of LMP1 on the balance of Bcl-2 and Bax ratio may play a role in inducing susceptibility to cisplatin-induced cell death. These results demonstrated that LMP1 did not confer growth advantage in CNE2 cells, suggesting that expression of LMP1 may not be crucial in sustaining cell growth in established cell lines. Alternatively, LMP1 alone may not be sufficient to facilitate nasopharyngeal carcinoma cell growth and additional oncogenic factors may be needed along with LMP1 in modulating the malignant property of nasopharyngeal carcinoma.
Liu
Yu
Y
Department of Anatomy, Faculty of Medicine, University of Hong Kong, Hong Kong, People's Republic of China.
Wang
Xianghong
X
Lo
Angela K F
AK
Wong
Yong Chuan
YC
Cheung
Annie L M
AL
Tsao
Sai Wah
SW
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division; D002945:Cisplatin / Q000494:pharmacology*; D004268:DNA-Binding Proteins; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014763:Viral Matrix Proteins; D051028:bcl-2-Associated X Protein; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D002945:Cisplatin