Regulation of bcl-2, bcl-XL and bax in the control of apoptosis by hematopoietic cytokines and dexamethasone.
Treatment of M1 myeloid leukemic cells with interleukin 6 (IL-6) or dexamethasone (DEX), both of which induce differentiation in these cells, down- regulated expression of the apoptosis-suppressing gene bcl-2 and the apoptosis- promoting gene bax but up-regulated expression of the apoptosis-suppressing gene bcl-XL. There was a higher expression of bcl-XL in cells treated with DEX or DEX plus IL-6 compared to cells treated with IL-6 alone. The alternatively spliced bcl-X gene, bcl-Xs, which interferes with the action of bcl-2, was not expressed. Treatment with IL-6 increased the susceptibility of these cells to induction of apoptosis by Adriamycin or cycloheximide, but treatment with DEX or with IL-6 and DEX did not. Withdrawal of DEX after up-regulation of bcl-XL resulted in a decrease in bcl-XL expression and a concomitant increase in cell susceptibility to induction of apoptosis. Another myeloid leukemia that shows barely detectable expression of bcl-2 also showed up-regulated expression of bcl-XL but no change in bax after induction of differentiation with granulocyte- macrophage colony-stimulating factor, and this reduced cell susceptibility to induction of apoptosis by Adriamycin or cycloheximide. The results indicate that the related apoptosis-regulating genes bcl-2, bcl-XL, and bax are differently regulated and that up-regulation of bcl-XL expression may compensate for down- regulation of bcl-2 in the balance between genes that control apoptosis.
- PubMed
- Europe PMC
- Cell Growth Differ 6:647-653 ()