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BCL-2 expression and mitochondrial activity in leukemic cells with
different sensitivity to glucocorticoid-induced apoptosis
LA Smets, J Van den Berg, D Acton, B Top, H Van Rooij and M Verwijs-Janssen
Division of Experimental Therapy, The Netherlands Cancer Institute,
Amsterdam.
The present study investigates the relationship between mitochondrial
activity and the expression of the BCL-2 gene in a panel of six human and
murine leukemia/lymphoma cell lines. The cell lines all contained normal
glucocorticoid receptors but differed widely in sensitivity to
dexamethasone, ranging from very sensitive S49 lymphoma to completely
resistant HL-60 acute leukemia cells. In this panel, 10- to 15-fold
differences in basal adenosine triphosphate (ATP) content and adenosine
diphosphate (ADP)/ATP ratio were correlated with up to fivefold differences
in bcl-2 protein (in human cells) and approximately 25-fold difference in
bcl-2 mRNA content (all cell lines). Moreover, ATP content and BCL-2 gene
expression were inversely correlated with glucocorticoid sensitivity and
cell cycle length. In resistant cell lines, sensitivity to dexamethasone
was restored by the mitochondrial inhibitors rotenone and
meta-iodobenzylguanidine. This sensitization was not accompanied by
detectable reductions in bcl-2 mRNA or protein content, suggesting that the
inhibitors were capable of overriding BCL- 2-mediated inhibition of
apoptosis. Increased mitochondrial activity and (overexpressed) BCL-2
appeared closely related properties of glucocorticoid-resistant cells,
sharing common cellular targets in hormone-induced apoptosis.
Volume 84,
Issue 5,
pp. 1613-1619,
09/01/1994
Copyright © 1994 by The American Society of Hematology
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