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Article: High level expression of ΔN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)?

TitleHigh level expression of ΔN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)?
Authors
Issue Date2000
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2000, v. 19 n. 30, p. 3439-3444 How to Cite?
AbstractUndifferentiated nasopharyngeal carcinoma (NPC) is an epithelial malignancy that is consistently associated with Epstein-Barr virus (EBV) but which very rarely has p53 gene mutations in primary tumours. Since the tumour suppressor p53 is mutated in most human cancers or the wild type protein is inactivated in a significant number of the remainder, here we have investigated cellular factors that could compromise p53 function in primary NPC. Twenty-five primary tumours were judged to carry only wild type p53 by SSCP analysis of all exons and sequence determination of exons 4-9. Only one tumour was found to express significant levels of hMdm2 and in 24/25 there were no detectable mutations or deletions in exons 1β and 2 of the p14(ARF) gene. However, immunohistochemistry consistently revealed that all the tumour cells express substantial amounts of the p53-related protein p63. Semi-quantitative RT-PCR analysis of mRNA from tumour biopsies showed that the dominant species expressed was invariably the truncated ΔN-isotype. Since this can block p53-mediated transactivation, it is potentially a dominant-negative isoform. In normal nasopharyngeal epithelium the distribution of p63 was restricted to the proliferating basal and suprabasal layers. We suggest that ΔN-p63 is a good candidate as a suppressor of wild type p53 function in these tumours and also that it may prove to be a valuable diagnostic marker for undifferentiated NPC.
Persistent Identifierhttp://hdl.handle.net/10722/148215
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCrook, Ten_US
dc.contributor.authorNicholls, JMen_US
dc.contributor.authorBrooks, Len_US
dc.contributor.authorO'nions, Jen_US
dc.contributor.authorAllday, MJen_US
dc.date.accessioned2012-05-29T06:11:33Z-
dc.date.available2012-05-29T06:11:33Z-
dc.date.issued2000en_US
dc.identifier.citationOncogene, 2000, v. 19 n. 30, p. 3439-3444en_US
dc.identifier.issn0950-9232en_US
dc.identifier.urihttp://hdl.handle.net/10722/148215-
dc.description.abstractUndifferentiated nasopharyngeal carcinoma (NPC) is an epithelial malignancy that is consistently associated with Epstein-Barr virus (EBV) but which very rarely has p53 gene mutations in primary tumours. Since the tumour suppressor p53 is mutated in most human cancers or the wild type protein is inactivated in a significant number of the remainder, here we have investigated cellular factors that could compromise p53 function in primary NPC. Twenty-five primary tumours were judged to carry only wild type p53 by SSCP analysis of all exons and sequence determination of exons 4-9. Only one tumour was found to express significant levels of hMdm2 and in 24/25 there were no detectable mutations or deletions in exons 1β and 2 of the p14(ARF) gene. However, immunohistochemistry consistently revealed that all the tumour cells express substantial amounts of the p53-related protein p63. Semi-quantitative RT-PCR analysis of mRNA from tumour biopsies showed that the dominant species expressed was invariably the truncated ΔN-isotype. Since this can block p53-mediated transactivation, it is potentially a dominant-negative isoform. In normal nasopharyngeal epithelium the distribution of p63 was restricted to the proliferating basal and suprabasal layers. We suggest that ΔN-p63 is a good candidate as a suppressor of wild type p53 function in these tumours and also that it may prove to be a valuable diagnostic marker for undifferentiated NPC.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_US
dc.relation.ispartofOncogeneen_US
dc.subject.meshCarrier Proteins - Geneticsen_US
dc.subject.meshCyclin-Dependent Kinase Inhibitor P16en_US
dc.subject.meshDna-Binding Proteinsen_US
dc.subject.meshGene Expression Regulation, Neoplasticen_US
dc.subject.meshGenes, Tumor Suppressoren_US
dc.subject.meshHumansen_US
dc.subject.meshMembrane Proteinsen_US
dc.subject.meshNasopharyngeal Neoplasms - Genetics - Pathologyen_US
dc.subject.meshNuclear Proteinsen_US
dc.subject.meshPhosphoproteins - Genetics - Metabolismen_US
dc.subject.meshProtein Isoforms - Genetics - Metabolismen_US
dc.subject.meshProteins - Geneticsen_US
dc.subject.meshProto-Oncogene Proteins - Biosynthesisen_US
dc.subject.meshProto-Oncogene Proteins C-Mdm2en_US
dc.subject.meshTrans-Activatorsen_US
dc.subject.meshTranscription Factorsen_US
dc.subject.meshTumor Suppressor Protein P14arfen_US
dc.subject.meshTumor Suppressor Protein P53 - Biosynthesis - Geneticsen_US
dc.subject.meshTumor Suppressor Proteinsen_US
dc.titleHigh level expression of ΔN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)?en_US
dc.typeArticleen_US
dc.identifier.emailNicholls, JM: nicholls@pathology.hku.hken_US
dc.identifier.authorityNicholls, JM=rp00364en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.pmid10918601en_US
dc.identifier.scopuseid_2-s2.0-0034644195en_US
dc.identifier.hkuros56462-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034644195&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume19en_US
dc.identifier.issue30en_US
dc.identifier.spage3439en_US
dc.identifier.epage3444en_US
dc.identifier.isiWOS:000088198100012-
dc.publisher.placeUnited Kingdomen_US
dc.customcontrol.immutablesml 130621-

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