Acquired expression of transcriptionally active p73 in hepatocellular carcinoma cells

Oncogene. 2001 Aug 23;20(37):5111-7. doi: 10.1038/sj.onc.1204669.


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 DeltaN-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 DeltaN-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 p14(ARF) 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 DeltaN-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Western
  • COS Cells
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • DNA, Complementary / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Genes, Dominant
  • Genes, Tumor Suppressor
  • Humans
  • Liver / metabolism
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism*
  • Phenotype
  • Protein Isoforms
  • Protein Structure, Tertiary
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic*
  • Tumor Cells, Cultured
  • Tumor Protein p73
  • Tumor Suppressor Proteins


  • DNA, Complementary
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Protein Isoforms
  • RNA, Messenger
  • TP73 protein, human
  • Trp73 protein, mouse
  • Tumor Protein p73
  • Tumor Suppressor Proteins

Associated data

  • GENBANK/AH007820
  • GENBANK/AL136528
  • GENBANK/Y19235