title: Effects of human papillomavirus (HPV) type 16 oncoproteins on the expression of involucrin in human keratinocytes.
abstract: BACKGROUND
  The human papillomavirus (HPV) life cycle is closely linked to keratinocyte differentiation. Oncogenic HPV infection has been shown to hamper the normal differentiation of keratinocytes; however, the underlying mechanisms responsible for this phenomenon are yet to be clarified. Here, we aimed to study the effects of HPV16 E6 and E7 oncogenes on the expression of involucrin (IVL), an established marker of keratinocyte differentiation, in human foreskin keratinocyte (HFK) cells.
  
  
  RESULTS
  The differentiation of HFK cells by serum and high calcium significantly increased both the mRNA and the protein levels of IVL. The E6 and E7 oncoproteins of HPV16 together caused strong down-regulation of IVL mRNA and protein both in proliferating and in differentiating HFK cells. To study the effects of HPV oncogenes on the IVL promoter, we made transient transfection assays and luciferase tests and found that HPV 16 E6 but not E7 repressed IVL promoter activity in proliferating HFK cells. The inhibitory effect of HPV 16 E6 on the human IVL promoter could be localised to the proximal regulatory region (PRR) of the gene.
  
  
  CONCLUSIONS
  These results suggest that the down-regulation of IVL promoter activity by HPV 16 E6 significantly contribute to the inhibition of endogenous IVL expression by the HPV 16 oncoproteins. In contrast, the down-regulation of endogenous IVL expression by HPV16 E7 is probably not caused by a direct and specific effect of E7 on the IVL promoter.
authors.affiliation: Department of Medical Microbiology, Medical and Health Science Centre, University of Debrecen, 4032 Debrecen, Nagyerdei krt, 98, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Gyöngyösi
authors.forename: Anita
authors.initials: A
authors.lastname: Szalmás
authors.forename: Annamária
authors.initials: A
authors.lastname: Ferenczi
authors.forename: József
authors.initials: J
authors.lastname: Kónya
authors.forename: Lajos
authors.initials: L
authors.lastname: Gergely
authors.forename: György
authors.initials: G
authors.lastname: Veress
mesh_terms: D002478:Cells, Cultured; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000821:virology*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000096:biosynthesis*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011498:Protein Precursors; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; C032253:involucrin