Apoptosis: basic concepts and potential significance in human cancer.
Numerous factors trigger or repress apoptosis (genetically mediated individual cell death). The details of signal transduction pathways and regulation of apoptosis by numerous oncogene and tumor suppressor gene products are not fully understood. Bcl-2 inhibits apoptosis induction by a variety of stimuli. Caspases are the basic effectors of apoptosis, leading ultimately to fragmentation of DNA, at which stage apoptosis can be identified. Apoptosis affects scattered individual cells that have extremely dense nodular, beaded, or crescentic chromatin, and differs morphologically, biochemically, and topographically from necrosis. Apoptosis is a negative growth-regulating mechanism in cancer, and its extent varies with tumor type. Apoptosis reflects tumor cell kinetics; aggressive tumors often show conspicuous apoptosis, and there are significant linear correlations between apoptotic and mitotic indices in many tumor types. The relative importance of p53, c-Myc, Rb, and the Bcl-2 homologs in the regulation of apoptosis in different human cancers is not clear. Further pathologic investigations on apoptosis in human cancer are needed to reaffirm recent experimental findings and to explain more fully the regulation and biological significance of apoptosis in vivo.
Staunton
M J
MJ
Department of Histopathology, St James's Hospital and Trinity College Medical School, Dublin, Ireland.
Gaffney
E F
EF
D017209:Apoptosis; D016147:Genes, Tumor Suppressor; D006801:Humans; D008854:Microscopy, Electron; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D009857:Oncogenes