[Apoptosis, tumor phenotype and pathogenesis of malignant tumors].

Abstract

Integrity of multicellular organisms is maintained by balance between cell proliferation and programmed cell death (apoptosis). Apoptosis is programmed cell death by regulated active process characterized by specific morphological and biochemical changes, whereas necrosis is a passive and genetically uncontrolled process followed by an inflammatory reaction of surrounding tissue. Suppression of apoptosis may contribute to the development of malignant tumours by means of accumulation of continuously proliferating cells and disruption of elimination of genetically altered cells with increasing malignant potential. Cell proliferation, differentiation and apoptosis are regulated by p16-cyclin D1-CDK4-Rb and p19ARF-p53-p21WAF1 pathways, which interact through multifunctional genes Rb and p53. Malignant tumours result from an accumulation of mutations of oncogenes, tumour-suppressor genes, pro-apoptotic and anti-apoptotic genes or from functional alterations of protein products of these genes as well. That results in dysregulation of the cell cycle and apoptosis and in the development of other signs of tumour phenotype (chromosomal instability, disruption of DNA repair, disruption of cell-cell communications and interactions between cells and extracellular matrix, suppression of the cell differentiation and replicative senescence, angiogenesis and changes in cell motile activity). Alteration of apoptosis, and/or genes involved in its regulation, is expressed in most manifestations of tumour phenotype. Thus, alteration of apoptosis strongly affects biological properties of malignant tumours and efficacy of their multimodal therapy. Present-day multimodal therapy of malignant tumours is specifically aimed at promoting the rate of apoptosis within tumours.