Acquired expression of transcriptionally active p73 in hepatocellular carcinoma cells

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dc.citation.epage5117en_US
dc.citation.issueNumber37en_US
dc.citation.spage5111en_US
dc.citation.volumeNumber20en_US
dc.contributor.authorSayan, A. E.en_US
dc.contributor.authorSayan, B. S.en_US
dc.contributor.authorFindikli, N.en_US
dc.contributor.authorOzturk, M.en_US
dc.date.accessioned2016-02-08T10:34:50Z
dc.date.available2016-02-08T10:34:50Z
dc.date.issued2001en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractp53 and p73 proteins activate similar target genes and induce apoptosis and cell cycle arrest. However, p53, but not p73 is considered a tumour-suppressor gene. Unlike p53, p73 deficiency in mice does not lead to a cancer-prone phenotype, and p73 gene is not mutated in human cancers, including hepatocellular carcinoma. Here we report that normal liver cells express only ΔN-p73 transcript forms giving rise to the synthesis of N-terminally truncated, transcriptionally inactive and dominant negative p73 proteins. In contrast, most hepatocellular carcinoma cells express TA-p73 transcript forms encoding full-length and transcriptionally active p73 proteins, in addition to ΔN-p73. We also show that together with the acquired expression of TA-p73, the 'retinoblastoma pathway' is inactivated, and E2F1-target genes including cyclin E and p14ARF are activated in hepatocellular carcinoma. However, there was no full correlation between 'retinoblastoma pathway' inactivation and TA-p73 expression. Most TA-p73-expressing hepatocellular carcinoma cells have also lost p53 function either by lack of expression or missense mutations. The p73 gene, encoding only ΔN-p73 protein, may function as a tumour promoter rather than a tumour suppressor in liver tissue. This may be one reason why p73 is not a mutation target in hepatocellular carcinoma.en_US
dc.identifier.doi10.1038/sj.onc.1204669en_US
dc.identifier.issn0950-9232
dc.identifier.urihttp://hdl.handle.net/11693/24820
dc.language.isoEnglishen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/sj.onc.1204669en_US
dc.source.titleOncogeneen_US
dc.subjectCyclin Een_US
dc.subjectLiver canceren_US
dc.subjectp14ARFen_US
dc.subjectp16INK4aen_US
dc.subjectp73en_US
dc.subjectRetinoblastomaen_US
dc.subjectCyclin Een_US
dc.titleAcquired expression of transcriptionally active p73 in hepatocellular carcinoma cellsen_US
dc.typeArticleen_US

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