BAX SUPPRESSES TUMORIGENESIS AND STIMULATES APOPTOSIS IN-VIVO

The protein p53 is a key tumour-suppressor, as evidenced by its freque nt inactivation in human cancers. Animal models have indicated that at tenuation of p53-dependent cell death (apoptosis) can contribute to bo th the initiation and progression of cancer, but the molecular mechani sms are unknown, Although p53-mediated transcriptional activation is o ne possible explanation, none of the known p53-responsive genes has be en 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, Inact ivation of p53 causes a dramatic acceleration of tumour growth owing t o a reduction in apoptosis of over ninety per cent(1). We show that p5 3-dependent expression of bax is induced in slow-growing apoptotic tum ours. Moreover, tumour growth is accelerated and apoptosis drops by fi fty per cent in Bax-deficient mice, indicating that it is required for a full p53-mediated response. To our knowledge this is the first demo nstration that Bax acts as a tumour suppressor, and our findings indic ate that Bax could be a component of the p53-mediated apoptotic respon se in this system.