c-Myc does not prevent glucocorticoid-induced apoptosis of human leukemic lymphoblasts

Due to their growth arrest- and apoptosis-inducing ability, glucocorticoids (GC) are widely used in the therapy of various lymphoid malignancies, The signal transduction pathways leading to this clinically-relevant form of ap optosis have, however, not been sufficiently elucidated. GC bind to their s pecific receptor, a ligand-activated transcription factor of the Zn-finger type, that activates or represses transcription of GC-responsive genes. Pre vious studies in leukemia cells suggested that transcriptional repression o f c-myc expression might be the crucial event in CC-induced apoptosis, alth ough in other systems, c-Myc apparently increased the sensitivity to cell-d eath inducers. To address this controversy, we stably transfected the GC-se nsitive human T-ALL cell Line CEM-C7H2 with constructs allowing tetracyclin e-regulated expression of c-Myc. Subsequent analyses of these cell lines sh owed that overexpression of c-Myc per se had little, if any, effect on cell viability, although it rendered the cells more sensitive to apoptosis indu ced by low serum, confirming the functionality of the expressed transgene, More importantly, however, when the cells were treated with GC in the prese nce of exogenous c-Myc, they underwent apoptosis exceeding that in cells tr eated in the absence of transgenic c-Myc. The data indicate that c-myc down regulation is not critical for induction of cell-death by GC in this system , and support the notion that c-Myc sensitizes cells to apoptosis-inducing agents.