Apoptosis and cancer.

Programmed cell death or apoptosis is a process of active cell death charac terized by cell shrinkage and cell fragmentation into apoptotic bodies. Apo ptosis deregulation in excess or in defect respectively contributes to dege nerative and proliferative diseases. Proteases, specially cysteinyl-asparta ses or caspases, are the main apoptosis executionners, leading to cytoskele ton and membrane damage, and to chromatin cleavage into nucleosomes. Mitoch ondrion control (by translocation of activators, the Apafs), cytoplasma pro tein /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 dam age and p53 activation; regulation of apoptotic and anti-apoptotic product expression) can initiate apoptosis, and can be available in cells in equili brium with protective pathways (abl and PKC activities). Each cell would co mmit suicide or would become apoptosis resistant (cancerogenesis) according to its own enzymatic equipement. After emergence of apoptosis resistant ce llular clones, genetically heterogeneous tumor development results from equ ilibrium between cellular proliferation and death. Identification of apopto sis regulators has led to validate new pronostic markers (p53, belt), and t o provide therapeutic apoptosis strategy in cancer.