Apoptosis and cancer.

Programmed cell death or apoptosis is a process of active cell death characterized by cell shrinkage and cell fragmentation into apoptotic bodies. Apoptosis deregulation in excess or in defect respectively contributes to degenerative and proliferative diseases. Proteases, specially cysteinyl-aspartases or caspases, are the main apoptosis executionners, leading to cytoskeleton and membrane damage, and to chromatin cleavage into nucleosomes. Mitochondrion control (by translocation of activators, the Apafs), cytoplasma protein /protein interactions and protein phosphorylations by Jun Kinases are involved in the enzyme activity regulation. Different pathways (exogeneous signal transduction with ceramide signalling and kinase activation; DNA damage and p53 activation; regulation of apoptotic and anti-apoptotic product expression) can initiate apoptosis, and can be available in cells in equilibrium with protective pathways (abl and PKC activities). Each cell would commit suicide or would become apoptosis resistant (cancerogenesis) according to its own enzymatic equipement. After emergence of apoptosis resistant cellular clones, genetically heterogeneous tumor development results from equilibrium between cellular proliferation and death. Identification of apoptosis regulators has led to validate new pronostic markers (p53, belt), and to provide therapeutic apoptosis strategy in cancer.