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[Bcl-2 tumor suppressor as a possible mediator between genotoxic stress and disturbance in hormonal homeostasis].

Overexpression of tumor suppressor gene bcl-2 plays an important role in cellular resistance to apoptosis caused by various factors including glucocorticoids. In this study, the role of bcl-2 in glucocorticoid-mediated negative feedback regulation has been investigated. Transient transfection of bcl-2 into murine corticotrope AtT-20 cells resulted in significant resistance of proopiomelanocortin gene expression and ACTH secretion to down-regulation by dexamethasone. Bcl-2 revealed its activity mostly in the presence of saturating concentrations of dexamethasone (100 nM-1 mM). Overexpression of bcl-1 interfered with the receptor-mediated glucocorticoid activity and appeared to be relatively specific towards expression of proopiomelanocortin/ACTH. The data suggest a novel function of bcl-2 as a factor capable of regulating hormonal homeostasis. Thus, bcl-2 may be involved in hormonal and metabolic response to genotoxic stress, the phenomenon which was earlier defined as carcinogenic aging.