[Transformation function of human bronchial epithelial cell by latent membrane protein1 encoded by Epstein-Barr virus gene].
OBJECTIVE
Although some results show that latent membrane protein 1 (LMP1) may play an important role in the development of epithelium-derived tumors. There are few studies on the relationship between LMP1 and normal epithelial cell. So this study was designed to evaluate the effect of EBV LMP1 on cell transformation in human bronchial epithelial (HBE) cell and its mechanism.


METHODS
Retrovirus expression vectors (LMP1 and LMP1+hTERT) were transfected into HBE cells and selected with the appropriate drugs to get resistant cells. The biological characteristics were studied by cell growth curve, colony formation analysis, and the determination of telomerase activity and protein expression of Cyclin A, p21, and CDK4.


RESULTS
wt-LMP1 together with hTERT gene transfected cells grew rapidly than HBE/wt-LMP1 cells. Soft agar plating rates of HBE/wt-LMP1-hTERT, HBE/wt-LMP1, and HBE/pLNSX+pBabe were 22.98%, 16.94%, and 8.85%, respectively. The activities of telomerase were 2.825, 2.441, and 1.876, respectively. In addition, there was no difference of protein expression of CDK4 among these groups. However, HBE/wt-LMP1-hTERT and HBE/wt-LMP1 cells had low-level p21 and high-level cyclin A protein expression than the vector groups.


CONCLUSIONS
The results suggest that LMP1 is in tandem with hTERT in promoting cell proliferation and transformation through modulating expression level of cyclin A and p21 protein.
Zhang
Xiao-Peng
XP
Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, PR China.
He
Zhi-Min
ZM
He
Chun-Mei
CM
Hou
De-Fu
DF
Li
Cui
C
Chen
Zhu-Chu
ZC
D015153:Blotting, Western; D001980:Bronchi / Q000473:pathology*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D019925:Cyclin A / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D004268:DNA-Binding Proteins; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000209:etiology*; D019098:Telomerase / Q000032:analysis; D014763:Viral Matrix Proteins / Q000032:analysis / Q000502:physiology*
C493956:CDKN1A protein, human; D019925:Cyclin A; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D019098:Telomerase