Suppression of c-myc is a critical step in glucocorticoid-induced human leukemic cell lysis.

Abstract

Glucocorticoids evoke cytolysis in clonal human leukemic CEM-C7 cells. Suppression of c-myc mRNA by dexamethasone closely correlates with cell lysis only in CEM clones with both glucocorticoid receptor and intact lysis functions. We tested the theory that c-myc repression is essential for glucocorticoid-induced lymphocytolysis by preventing down-regulation of c-myc gene in the presence of dexamethasone and by reducing c-myc mRNA levels with antisense oligonucleotides. We find that sustained expression of c-myc provides resistance to dexamethasone-induced lysis, and antisense c-myc oligomers induce cell lysis. The lethal effects of dexamethasone in these leukemic cells appear to involve reduction of c-myc below the levels required to maintain cellular growth and integrity.