Apoptosis and cancer mechanisms.

For nearly two decades, studies in the cancer research field focussed on identifying genes that act as positive and negative regulators of cell growth. Only relatively recently was it recognized that the regulation of cell death (apoptosis) is also an important modulator of tumorigenesis. At least two genes linked to human cancers, BCL2 and TP53, have been shown to regulate apoptosis. The correlation between apoptosis modulating genes and human tumours raises an important question as to how dysregulation of apoptosis contributes to neoplastic transformation and malignant cell growth. Cell culture studies have clearly demonstrated that TP53 can induce and BCL2 can suppress apoptosis in response to various stimuli. Studies of mammalian viruses, which possess mechanisms for both inducing and evading apoptosis, have also extended our understanding of this process. On the basis of such findings, several animal models have been developed which begin to address the role of apoptosis regulation in tumorigenesis. This chapter discusses those animal models, focussing on bcl-2 (and its relatives) and p53.