title: Transcriptional regulation of genes involved in keratinocyte differentiation by human papillomavirus 16 oncoproteins.
abstract: The life cycle of human papillomaviruses (HPVs) is strictly linked to the differentiation of their natural host cells. The HPV E6 and E7 oncoproteins can delay the normal differentiation program of keratinocytes; however, the exact mechanisms responsible for this have not yet been identified. The goal of this study was to investigate the effects of HPV16 oncoproteins on the expression of genes involved in keratinocyte differentiation. Primary human keratinocytes transduced by LXSN (control) retroviruses or virus vectors expressing HPV16 E6, E7 or E6/E7 genes were subjected to gene expression profiling. The results of microarray analysis showed that HPV 16 E6 and E7 have the capacity to downregulate the expression of several genes involved in keratinocyte differentiation. Quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to confirm the microarray data. To investigate the effects of the HPV oncoproteins on the promoters of selected keratinocyte differentiation genes, luciferase reporter assays were performed. Our results suggest that the HPV 16 E6 and/or E7 oncogenes are able to downregulate the expression of several genes involved in keratinocyte differentiation (such as desmocollin 1, keratin 4, S100 calcium-binding protein A8 and small proline-rich protein 1A), at least partially by downregulating their promoter activity. This activity of the HPV oncoproteins may have a role in the productive virus life cycle, and also in virus-induced carcinogenesis.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Debrecen, 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: Szilárd
authors.initials: S
authors.lastname: Póliska
authors.forename: József
authors.initials: J
authors.lastname: Kónya
authors.forename: György
authors.initials: G
authors.lastname: Veress
mesh_terms: D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D040501:Calgranulin A / Q000096:biosynthesis; D063646:Carcinogenesis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D051187:Desmocollins / Q000096:biosynthesis; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053527:Keratin-4 / Q000096:biosynthesis; D015603:Keratinocytes / Q000166:cytology* / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D018808:Transcription Factor AP-1 / Q000235:genetics; D014157:Transcription Factors / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic; D014161:Transduction, Genetic
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D040501:Calgranulin A; C081560:DSC1 protein, human; D051187:Desmocollins; C068651:E6 protein, Human papillomavirus type 16; D053527:Keratin-4; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16