title: Reconstruction of human papillomavirus type 16-mediated early-stage neoplasia implicates E6/E7 deregulation and the loss of contact inhibition in neoplastic progression.
abstract: Infection with human papillomavirus type 16 (HPV-16) can lead to low- or high-grade squamous intraepithelial lesions (LSIL or HSIL). Here we show that these in vivo disease states can be replicated in raft cultures of early-pass HPV-16 episomal cell lines, at both the level of pathology and the level of viral gene expression. A reduced responsiveness to cell-cell contact inhibition and an increase in E6/E7 activity correlated closely with phenotype. Similar deregulation is likely to underlie the appearance of LSIL or HSIL soon after infection.
authors.affiliation: Division of Virology, National Institute for Medical Research, London, United Kingdom.
authors.forename: Erin
authors.initials: E
authors.lastname: Isaacson Wechsler
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Ian
authors.initials: I
authors.lastname: Roberts
authors.forename: Emilio
authors.initials: E
authors.lastname: Pagliarulo
authors.forename: Deborah
authors.initials: D
authors.lastname: Jackson
authors.forename: Christina
authors.initials: C
authors.lastname: Untersperger
authors.forename: Nick
authors.initials: N
authors.lastname: Coleman
authors.forename: Heather
authors.initials: H
authors.lastname: Griffin
authors.forename: John
authors.initials: J
authors.lastname: Doorbar
mesh_terms: D002278:Carcinoma in Situ / Q000821:virology*; D002478:Cells, Cultured; D003260:Contact Inhibition; D005260:Female; D052162:Human papillomavirus 16 / Q000472:pathogenicity*; D006801:Humans; D066298:In Vitro Techniques; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D037521:Virulence Factors; C059731:oncogene protein E7, Human papillomavirus type 16