Expression of the HPV16 E7 gene generates proliferation in stratified squamous cell cultures which is independent of endogenous p53 levels.
Monolayer cultures of human foreskin and ectocervical epithelial cells were infected with retroviral vectors expressing HPV16 oncogenes, selected for G418 resistance, and cultured organotypically so that they reformed the fully differentiated, stratified squamous tissues from which they were originally derived. Expression of HPV16 E7 prevented cell cycle withdrawal in the suprabasal layers of these stratified cultures but had no effect on terminal differentiation. Cultures expressing E7 alone and those coexpressing E6 and E7 were identical in terms of suprabasal proliferation and terminal differentiation, but they differed in expression of the endogenous tumor suppressor protein p53. Immunohistochemically detectable p53 protein localized to the proliferative compartment in normal and E7-containing cultures but was undetectable in those cultures which coexpressed E6 and E7. This result suggests that E7-induced suprabasal proliferation is independent of the steady-state level of p53.
Blanton
R A
RA
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Coltrera
M D
MD
Gown
A M
AM
Halbert
C L
CL
McDougall
J K
JK
D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology*; D004790:Enzyme Induction; D004847:Epithelial Cells; D005260:Female; D005814:Genes, Viral; D006801:Humans; D008297:Male; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000502:physiology*; D009857:Oncogenes; D027383:Papillomaviridae / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D010413:Penis / Q000166:cytology*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000037:antagonists & inhibitors; D015678:Viral Structural Proteins / Q000235:genetics*
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D015678:Viral Structural Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D011505:Protein-Tyrosine Kinases