APOPTOSIS AND ITS ROLE IN TUMOR-GROWTH

Molecular genetic investigations show that in addition to BCL-2 genes mapped in humans on chromosome 18 there are other genes responsible fo r enhancement or inhibition or apoptosis (BAX, BAK, BAD, P-53, C-MYC, APO-1/FAS and C-FES, respectively). Growth factors, extracellular matr ix, CD-40-ligand, neutral amino acids, zink, estrogens, androgens belo ng to basic physiological inhibitors of apoptosis. Growth factors are the most potent antiapoptotic stimuli for normal hemopoiesis. Cytokine s SF, TPO, EPO, GM-CSF, G-CSF, M-CSF, IL-2, IL-3, IL-4, IL-10, alpha-I FN prevent apoptosis while such cytokines as IL-I, IL-4, IL-10, gamma- IFN, TFG and TNF induce apoptosis. Antitumor drugs are apoptosis induc ers, i.e. they cause death of tumor cells. The pattern of apoptosis in this case is similar to that used by physiological apoptosis inducers : stimulation of P-53 gene, modulation of BCL-2 genes, inclusion of FA S-receptor, activation of effector proteases and endonucleases, blocki ng of receptors of antiapoptotic growth factors and stimulation of pro apoptotic growth factors. Common reason of resistance of tumor cells t o drugs is mutation or deficiency of gene P-53 or overexpression of ge ne BCL-2 making cells unresponsible to all the proapoptotic stimuli. T he study of apoptosis mechanisms and methods of their regulation enabl es new interpretation of hemopoiesis, oncogenesis events, open perspec tives for advancements in tumor treatment.