Acquired expression of transcriptionally active p73 in hepatocellular carcinoma cells

A. E. Sayan, B. S. Sayan, N. Findikli, M. Ozturk

    Research output: Contribution to journalArticlepeer-review

    Abstract

    p53 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.
    Original languageEnglish
    Pages (from-to)5111-5117
    Number of pages6
    JournalOncogene
    Volume20
    Issue number37
    DOIs
    Publication statusPublished - 23 Aug 2001

    Keywords

    • Cyclin E
    • Liver cancer
    • p14ARF
    • p16INK4a
    • p73
    • Retinoblastoma

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