p51/p63, a novel p53 homologue, potentiates p53 activity and is a human cancer gene therapy candidate

J Gene Med. 2006 Sep;8(9):1121-30. doi: 10.1002/jgm.945.


Background: p51 (p73L/p63/p40/KET), a recently isolated novel p53 homologue, binds to p53-responsive elements to upregulate some p53 target genes and has been suggested to share partially overlapping functions with p53. p51 may be a promising candidate target molecule for anti-cancer therapy.

Methods: In this study, we adenovirally transduced p51A cDNA into human lung, gastric and pancreatic cancer cells and analyzed the intracellular function of p51 in anti-oncogenesis in vitro and in vivo.

Results: Overexpression of p51A revealed an anti-proliferative effect in vitro in all the cancer cells examined in this study. The anchorage-dependent and -independent cell growth of EBC1 cells carrying mutations in both p51 and p53 was suppressed and significant apoptosis following adenoviral transduction with p51 and/or p53 was seen. This growth suppression was cooperatively enhanced by the combined infection with adenoviral vectors encoding both p51 and p53. Furthermore, p51 activated several, but not all, p53-inducible genes, indicating that the mechanisms controlling p51- and p53-mediated tumor suppression differed.

Conclusions: Our observations indicate that, although p51 exhibited reduced anti-oncogenetic effects compared with p53, it cooperatively enhanced the anti-tumor effects of p53. Our results suggest that p51 functions as a tumor suppressor in human cancer cells in vitro and in vivo and may be useful as a potential tool for cancer gene therapy.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Apoptosis
  • Base Sequence
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Proliferation
  • Colony-Forming Units Assay
  • DNA Primers / genetics
  • DNA-Binding Proteins / genetics*
  • Female
  • Genes, p53*
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Humans
  • Lac Operon
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy
  • Trans-Activators / genetics*
  • Transcription Factors
  • Transduction, Genetic
  • Transplantation, Heterologous
  • Tumor Suppressor Proteins / genetics*


  • DNA Primers
  • DNA-Binding Proteins
  • TP63 protein, human
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Proteins