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  • Original Paper
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Acquired expression of transcriptionally active p73 in hepatocellular carcinoma cells

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.

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Abbreviations

HCC:

hepatocellular carcinoma

RB1:

retinoblastoma gene

pRb:

retinoblastoma protein

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Acknowledgements

This work was supported by a grant from TUBITAK (Turkey). We would like to thank B Carr (University of Pittsburgh, PA, USA) for providing Hep40 and Hep3B-TR cell lines, D Bellet (Institut Gustave Roussy, France) for JAR13 antibody, R Cetin-Atalay for critical reading of the manuscript, T Cagatay for DNA sequencing work, C Akcali's group for animal surgery, and G Tuncman for help in RNA studies.

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Correspondence to Mehmet Ozturk.

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Sayan, A., Sayan, B., Findikli, N. et al. Acquired expression of transcriptionally active p73 in hepatocellular carcinoma cells. Oncogene 20, 5111–5117 (2001). https://doi.org/10.1038/sj.onc.1204669

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