Bax suppresses tumorigenesis and stimulates apoptosis in vivo

Nature. 1997 Feb 13;385(6617):637-40. doi: 10.1038/385637a0.


The protein p53 is a key tumour-suppressor, as evidenced by its frequent inactivation in human cancers. Animal models have indicated that attenuation of p53-dependent cell death (apoptosis) can contribute to both the initiation and progression of cancer, but the molecular mechanisms are unknown. Although p53-mediated transcriptional activation is one possible explanation, none of the known p53-responsive genes has been shown to function in p53-dependent apoptosis. Here we test the role of the death-promoting gene bax in a transgenic mouse brain tumour, a model in which p53-mediated apoptosis attenuates tumour growth. Inactivation of p53 causes a dramatic acceleration of tumour growth owing to a reduction in apoptosis of over ninety per cent. We show that p53-dependent expression of bax is induced in slow-growing apoptotic tumours. Moreover, tumour growth is accelerated and apoptosis drops by fifty per cent in Bax-deficient mice, indicating that it is required for a full p53-mediated response. To our knowledge this is the first demonstration that Bax acts as a tumour suppressor, and our findings indicate that Bax could be a component of the p53-mediated apoptotic response in this system.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Brain Neoplasms / genetics
  • Choroid Plexus / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Transgenic
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-bcl-2*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology
  • bcl-2-Associated X Protein


  • Bax protein, mouse
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein