Alteration of cell-cycle regulatory proteins in human oral epithelial cells immortalized by HPV16 E6 and E7.
E6 and E7 oncoproteins from high-risk human papillomavirus (HPV) can transform cells in tissue culture and induce tumors in vivo by abrogating the cell-cycle checkpoint. To investigate the impact of HPV16 E6 and E7 on the cell-cycle regulatory machinery in oral epithelial cells, normal human oral epithelial cells were transfected with HPV16 E6 and E7 open reading frames, and alterations in cell-cycle regulatory proteins in cells expressing HPV16 E6 and E7 were analyzed. E6 and E7 expression results in immortalization of oral epithelial cells. E7 inactivates retinoblastoma protein (Rb) by forming complexes with hypophosphorylated Rb in immortalized oral epithelial cells. P53 and P21 protein levels were increased in immortalized cells compared to normal primary oral epithelial cells. Cyclin D1-cell-cycle-dependent kinase 4 binary association is disrupted in immortalized oral epithelial cells. These results indicate that E7 plays an important role in abrogation of cell-cycle regulation in oral epithelial cells, with E6 having a smaller impact. This suggests that the pathogenesis of HPV in oral epithelial cells differs from that in cervical epithelial cells.
Sdek
P
P
School of Stomatology, Shanghai Second Medical University, 639 Zhi-Zao-Ju Road, Shanghai 200011, PR China.
Zhang
Z Y
ZY
Cao
J
J
Pan
H Y
HY
Chen
W T
WT
Zheng
J W
JW
D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002461:Cell Line, Transformed / Q000821:virology; D002472:Cell Transformation, Viral / Q000502:physiology*; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology*; D052162:Human papillomavirus 16 / Q000472:pathogenicity*; D006801:Humans; D047468:Immunoprecipitation; D009061:Mouth Mucosa / Q000166:cytology; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C059731:oncogene protein E7, Human papillomavirus type 16; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4