Acquired expression of transcriptionally active p73 in hepatocellular carcinoma cells

Sayan, AE; Sayan, BS; Findikli, N; Ozturk, M

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.

Citation

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

• Journal Article Type: Article
• Publication Date: Aug 28, 2001
• Deposit Date: Feb 6, 2023
• Journal: Oncogene
• Print ISSN: 0950-9232
• Publisher: Nature Publishing Group
• Volume: 20
• Pages: 5111-5117
• DOI: https://doi.org/10.1038/sj.onc.1204669
• Publisher URL: https://doi.org/10.1038/sj.onc.1204669