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dc.contributor.authorDowen, S E
dc.contributor.authorNeutze, D M
dc.contributor.authorPett, M R
dc.contributor.authorCottage, A
dc.contributor.authorStern, Peter L
dc.contributor.authorColeman, N
dc.contributor.authorStanley, M A
dc.date.accessioned2009-09-23T14:32:26Z
dc.date.available2009-09-23T14:32:26Z
dc.date.issued2003-04-24
dc.identifier.citationAmplification of chromosome 5p correlates with increased expression of Skp2 in HPV-immortalized keratinocytes. 2003, 22 (16):2531-40 Oncogeneen
dc.identifier.issn0950-9232
dc.identifier.pmid12717429
dc.identifier.doi10.1038/sj.onc.1206296
dc.identifier.urihttp://hdl.handle.net/10541/82374
dc.description.abstractThe oncogenic HPVs immortalize primary genital keratinocytes in vitro and there is evidence that such lines represent suitable models to examine HPV-induced carcinogenesis. Early in vivo studies and more recent CGH analyses have revealed amplification of chromosome 5p in advanced stage carcinoma of the uterine cervix (CaCx). In the present study, a panel of established CaCx-derived cell lines were analysed by M-FISH to identify recurrent karyotypic abnormalities. Amplification of 5p was observed in 11 of 13 CaCx cell lines harbouring HR (high-risk) HPV. The region of 5p undergoing amplification was confirmed using human band-specific paints. The F-box protein Skp2 is present at 5p13 and its protein is present at increased levels in many cancers of an advanced stage. The HPV16-harbouring cell line W12 shows progressive morphological abnormality with in vitro passage, culminating in an invasive phenotype. The expression of Skp2 at different stages of this progression was investigated utilizing Western blot and TaqMan quantitative PCR. At medium to late passage, gain of 5p as an isochromosome was observed. Increased expression of Skp2 and a reduction in the expression of its target p27 correlated with increasing passage in this line.
dc.language.isoenen
dc.subject.meshCell Cycle Proteins
dc.subject.meshCell Line, Transformed
dc.subject.meshCell Transformation, Viral
dc.subject.meshChromosome Painting
dc.subject.meshChromosomes, Human, Pair 5
dc.subject.meshGene Amplification
dc.subject.meshHumans
dc.subject.meshIn Situ Hybridization, Fluorescence
dc.subject.meshKeratinocytes
dc.subject.meshPapillomaviridae
dc.subject.meshPrecipitin Tests
dc.subject.meshProliferating Cell Nuclear Antigen
dc.subject.meshS-Phase Kinase-Associated Proteins
dc.titleAmplification of chromosome 5p correlates with increased expression of Skp2 in HPV-immortalized keratinocytes.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. sally-dowen@hotmail.comen
dc.identifier.journalOncogeneen
html.description.abstractThe oncogenic HPVs immortalize primary genital keratinocytes in vitro and there is evidence that such lines represent suitable models to examine HPV-induced carcinogenesis. Early in vivo studies and more recent CGH analyses have revealed amplification of chromosome 5p in advanced stage carcinoma of the uterine cervix (CaCx). In the present study, a panel of established CaCx-derived cell lines were analysed by M-FISH to identify recurrent karyotypic abnormalities. Amplification of 5p was observed in 11 of 13 CaCx cell lines harbouring HR (high-risk) HPV. The region of 5p undergoing amplification was confirmed using human band-specific paints. The F-box protein Skp2 is present at 5p13 and its protein is present at increased levels in many cancers of an advanced stage. The HPV16-harbouring cell line W12 shows progressive morphological abnormality with in vitro passage, culminating in an invasive phenotype. The expression of Skp2 at different stages of this progression was investigated utilizing Western blot and TaqMan quantitative PCR. At medium to late passage, gain of 5p as an isochromosome was observed. Increased expression of Skp2 and a reduction in the expression of its target p27 correlated with increasing passage in this line.


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