Bax suppresses tumorigenesis and stimulates apoptosis in vivo

• DOI: 10.1038/385637a0
• Publication Date: 2003-08-12T02:22:49Z
• Authors: Chaoying Yin; C. Michael Knudson; Stanley J. Korsmeyer; Terry Van Dyke
• Keywords: Male; Mice, Inbred C3H; 0303 health sciences; Brain Neoplasms; Apoptosis; Mice, Transgenic; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins; Choroid Plexus; Animals; Female; Genes, Tumor Suppressor; Tumor Suppressor Protein p53; bcl-2-Associated X Protein

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.