[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.
Revskoĭ
S Iu
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N.N. Petrov Research Institute of Oncology, Ministry of Health of the RF, St. Petersburg, Russia.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000235:genetics; D006706:Homeostasis; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D011333:Pro-Opiomelanocortin / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D009153:Mutagens; D019253:Proto-Oncogene Proteins c-bcl-2; D011333:Pro-Opiomelanocortin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone