Bcl-2 expression and glucocorticoid-induced apoptosis of leukemic and lymphoma cells.
The lytic response of lymphoid cells to glucocorticoid hormones (GC) is prototypical of the induction of apoptosis: a special form of cellular demise for the removal of unwanted or redundant cells. Initiation and execution of a death programme are therefore major checkpoints in GC-sensitivity. Although Bcl-2 protein can prevent or delay apoptosis of lymphoma and leukemia cells, exposed to multiple cytotoxic agents, its antagonism of GC-induced apoptosis appears most critical in conferring resistance to corticosteroids. Moreover, Bcl-2 may modulate GC-signalling to apoptosis through its association with fundamental cellular processes such as energy state, Ca2+ homeostasis and transmembrane transport. However, this signalling pathway can also be interrupted by Bcl-2- independent mechanisms. This review discusses the various cellular and oncogenetic factors that control GC sensitivity of leukemia/lymphoma cells and proposes a hypothesis of how GC may induce a death programme, sensitive to blockade by Bcl-2.
Smets
L A
LA
Division of Experimental Therapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis, Amsterdam, The Netherlands.
van den Berg
J D
JD
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D017252:CD3 Complex / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D008214:Lymphocytes / Q000166:cytology*; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D014407:Tumor Cells, Cultured
D017252:CD3 Complex; D005938:Glucocorticoids; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D003907:Dexamethasone; D000255:Adenosine Triphosphate