Bax suppresses tumorigenesis and stimulates apoptosis in vivo

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.