SUMMARY

The bcl-2 gene provides a window on the basic cellular machinery of apoptosis or programmed cell death, a process involved in virtually all biologic events in multicellular organisms, but particularly relevant to neoplasia and development. bcl-2 gene function supports cell survival and appears to lie at a nodal point in pathways leading to activation or execution of apoptosis. Carcinogenesis may involve several steps at which cell death programs are normally activated and are bypassed in cancer cells, including apoptotic pathways activated by several oncogenes. Functional redundancy and the complexity of the regulation of cell survival are demonstrated by the less than expected phenotype of bcl-2 knockout mice and the cloning of several bcl-2 related genes, some of which promote cell death. The molecular function for bcl-2 is unknown, but several lines of evidence support a role in protection from oxidative stress. These studies suggest that many environmental perturbations and genetic pathways converge to disrupt a metabolic balance between oxidant generation and anti-oxidant defenses.

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