Changes in cervical keratinocyte gene expression associated with integration of human papillomavirus 16

Hdl Handle:
http://hdl.handle.net/10034/96634
Title:
Changes in cervical keratinocyte gene expression associated with integration of human papillomavirus 16
Authors:
Alazawi, William; Pett, Mark; Arch, Barbara N.; Scott, Laurie; Freeman, Tom; Stanley, Margaret A.; Coleman, Nicholas
Abstract:
Episomal integration is a critical event in human papillomavirus (HPV)-related oncogenesis, although little information is currently available concerning the effect of integration on the host transcriptome. Expression microarrays were used to investigate the effect of integration of HPV16 on gene expression in cervical keratinocytes, using the unique cell line model W12. W12 was generated from a cervical low-grade squamous intraepithelial lesion "naturally" infected with HPV16 and at low passage contains approximately 100 HPV16 episomes/cell. With passage in vitro, integration of viral episomes is associated with the development of phenotypic and genomic abnormalities resembling those seen in cervical neoplastic progression in vivo. The Affymetrix U95A oligonucleotide array that contains probes for 12,600 human transcripts was used and 85 genes from a range of host cell pathways that show changes in expression levels after integration of HPV16 were identified. A range of genes not previously described as being involved in cervical neoplastic progression were identified. Interestingly, integration is associated with up-regulation of numerous IFN-responsive genes, in comparison with a baseline of episomally infected cells. These genes include p48, a component of the primary regulator of the IFN response pathway, IFN-stimulated gene factor 3. The physical state of high-risk HPV may substantially influence the response to IFN in infected keratinocytes.
Affiliation:
Medical Research Council Cancer Cell Unit, MRC/Hutchison Research Centre, Cambridge ; Department of Pathology, University of Cambridge ; Institute of Public Health, Cambridge ; Medical Research Council Human Genome Mapping Resource Centre, Cambridge ; Medical Research Council Human Genome Mapping Resource Centre, Cambridge ; Department of Pathology, University of Cambridge ; Medical Research Council Cancer Cell Unit, MRC/Hutchison Research Centre, Cambridge/Department of Pathology, University of Cambridge
Citation:
Cancer Research, 62, 2002, pp. 6959-6965
Publisher:
American Association for Cancer Research
Journal:
Cancer Research
Publication Date:
1-Dec-2002
URI:
http://hdl.handle.net/10034/96634
Additional Links:
http://cancerres.aacrjournals.org
Type:
Article
Language:
en
Description:
This article is not available through ChesterRep. It can be accessed at http://cancerres.aacrjournals.org/cgi/reprint/62/23/6959
ISSN:
0008-5472
Sponsors:
This article was submitted to the RAE2008 for the University of Chester - Allied Health Professions and Studies.
Appears in Collections:
Biological Sciences

Full metadata record

DC FieldValue Language
dc.contributor.authorAlazawi, Williamen
dc.contributor.authorPett, Marken
dc.contributor.authorArch, Barbara N.en
dc.contributor.authorScott, Laurieen
dc.contributor.authorFreeman, Tomen
dc.contributor.authorStanley, Margaret A.en
dc.contributor.authorColeman, Nicholasen
dc.date.accessioned2010-04-16T08:18:51Zen
dc.date.available2010-04-16T08:18:51Zen
dc.date.issued2002-12-01en
dc.identifier.citationCancer Research, 62, 2002, pp. 6959-6965en
dc.identifier.issn0008-5472en
dc.identifier.urihttp://hdl.handle.net/10034/96634en
dc.descriptionThis article is not available through ChesterRep. It can be accessed at http://cancerres.aacrjournals.org/cgi/reprint/62/23/6959en
dc.description.abstractEpisomal integration is a critical event in human papillomavirus (HPV)-related oncogenesis, although little information is currently available concerning the effect of integration on the host transcriptome. Expression microarrays were used to investigate the effect of integration of HPV16 on gene expression in cervical keratinocytes, using the unique cell line model W12. W12 was generated from a cervical low-grade squamous intraepithelial lesion "naturally" infected with HPV16 and at low passage contains approximately 100 HPV16 episomes/cell. With passage in vitro, integration of viral episomes is associated with the development of phenotypic and genomic abnormalities resembling those seen in cervical neoplastic progression in vivo. The Affymetrix U95A oligonucleotide array that contains probes for 12,600 human transcripts was used and 85 genes from a range of host cell pathways that show changes in expression levels after integration of HPV16 were identified. A range of genes not previously described as being involved in cervical neoplastic progression were identified. Interestingly, integration is associated with up-regulation of numerous IFN-responsive genes, in comparison with a baseline of episomally infected cells. These genes include p48, a component of the primary regulator of the IFN response pathway, IFN-stimulated gene factor 3. The physical state of high-risk HPV may substantially influence the response to IFN in infected keratinocytes.en
dc.description.sponsorshipThis article was submitted to the RAE2008 for the University of Chester - Allied Health Professions and Studies.en
dc.language.isoenen
dc.publisherAmerican Association for Cancer Researchen
dc.relation.urlhttp://cancerres.aacrjournals.orgen
dc.subjecthuman papillomavirus 16en
dc.titleChanges in cervical keratinocyte gene expression associated with integration of human papillomavirus 16en
dc.typeArticleen
dc.contributor.departmentMedical Research Council Cancer Cell Unit, MRC/Hutchison Research Centre, Cambridge ; Department of Pathology, University of Cambridge ; Institute of Public Health, Cambridge ; Medical Research Council Human Genome Mapping Resource Centre, Cambridge ; Medical Research Council Human Genome Mapping Resource Centre, Cambridge ; Department of Pathology, University of Cambridge ; Medical Research Council Cancer Cell Unit, MRC/Hutchison Research Centre, Cambridge/Department of Pathology, University of Cambridgeen
dc.identifier.journalCancer Researchen
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