Intercellular induction of apoptosis through modulation of endogenous survival factor concentration: a review.

Fibroblasts constitutively express a functional apoptosis machinery which is under negative control by operationally defined endogenous survival factors. Oncogenic transformation causes a marked downmodulation of endogenous survival factor concentration which renders transformed cells more sensitive to various apoptosis stimuli compared to their nontransformed counterparts. Endogenous survival factors can be inactivated by reactive oxygen species (ROS). Endogenous survival factors are the ultimate targets for apoptosis-inducing factors derived from TGF-beta-triggered nontransformed cells during intercellular induction of apoptosis. During this control step of oncogenesis, endogenous survival factors in transformed cells are inactivated by ROS and the apoptosis machinery is released from negative control. This mechanism leads to the specific elimination of transformed cells. Our data show that the transformed state causes both the ability of the cells to perceive the apoptosis-inducing signal and a decrease in the concentration of endogenous survival factors. These two mechanisms are of central importance for the regulation of intercellular induction of apoptosis.