Cooperative interactions among p53, bcl-2 and Epstein-Barr virus latent membrane protein 1 in nasopharyngeal carcinoma cells.
Interactions among p53, bcl-2 and Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) in nasopharyngeal carcinoma (NPC) cells were evaluated by gene cotransfections. The data showed that bcl-2 expression was not only able to prevent the growth suppression induced by wild-type p53 but was also paradoxically able to inhibit the growth enhancement induced by mutant p53. Latent membrane protein 1 was shown to be capable of overcoming the growth inhibition induced by wild-type p53 and the synergistic cooperation with bcl-2 to enhance cellular growth. Latent membrane protein 1 could also cooperate with mutant p53 to provide a growth advantage for NPC cells. Most NPC revealed detectable overexpression of p53, and the majority of those were a wild type possibly responding to EBV infection. The coexpression of bcl-2 and LMP1 was thought to inhibit the growth suppression induced by wild-type p53 in NPC. But there was no associated expression between LMP1 and bcl-2 because we demonstrated that transfected LMP1 failed to induce bcl-2 expression in NPC cells in contrast to the findings in B cells. It is theorized that the cooperative expression of bcl-2 and LMP1 exists in the majority of NPC, while a minority of NPC have cooperative expression of LMP1 and mutant p53. Each cooperative interaction could play an important role in the development and progression of NPC.
Sheu
Lai-Fa
LF
Department of Pathology, Tri-Service General Hospital, National Defense Center, Taipei, Taiwan, Republic of China. laifakimo@yahoo.com.tw
Chen
An
A
Lee
Herng-Sheng
HS
Hsu
Hsue-Yin
HY
Yu
Da-Shung
DS
D000230:Adenocarcinoma / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D014763:Viral Matrix Proteins