Epstein-Barr virus LMP1 initiates cell proliferation and apoptosis inhibition via regulating expression of Survivin in nasopharyngeal carcinoma.
Pathways controling cell proliferation and cell survival require flexible adaptation to environmental stress. Our previous studies showed that latent membrane protein1 (LMP1) encoded by Epstein-Barr virus (EBV) could trigger the expression of Survivin, an apoptosis inhibitor and essential regulator of mitosis. The aim of the work was to analyze the role of Survivin signal pathway in mediating effects triggered by LMP1.


METHODS
Tet-on LMP1 HNE2, a tetracycline-regulated LMP1-expression nasopharyngeal carcinoma cell line, was used as cell model. The subcellular location of Survivin was detected by indirect immunofluorescence and Western-blotting assay. Using Ab-knock-out and gene transfection, we introduced anti-sense PS-ODN-Survivin and anti-body to Survivin into the Tet-on LMP1 HNE2, and then the apoptosis and the proliferation of cells were analyzed by flow cytometry, cell colony formation and detection of caspase-3. The results show that upon induction of LMP1 expression, the expression of Survivin in nucleus, level of phosphorylated retinoblastoma gene (Rb), the number of cells in S stage of cell cycle, and the cell colony formation rate were higher than those without LMP1 induction; if the expression of Survivin and the nucleus translocation of Survivin were knocked by introduction of anti-sense PS-ODN-Survivin and anti-Survivin-antibodies respectively, apoptosis rates and the activity of caspase-3 increased.


CONCLUSIONS
LMP1 could trigger the nucleus translocation of Survivin, which led to the shift of S stage and cell proliferation. LMP1 may promote cell proliferation and inhibits apoptosis via Survivin signal pathway.
Clinic Laboratory, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Tang
T
Faqing
Hu
H
Zhi
Yin
Y
Liqun
Tang
T
Min
Gu
G
Huanhua
Deng
D
Xiyun
Cao
C
Ya
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism; D016196:S Phase; D015398:Signal Transduction / Q000502:physiology; D013347:Subcellular Fractions; D000077022:Survivin; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
C107489:BIRC5 protein, human; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D016160:Retinoblastoma Protein; D000077022:Survivin; D014763:Viral Matrix Proteins; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases