Constitutive expression of ectopic c-Myc delays glucocorticoid-evoked apoptosis of human leukemic CEM-C7 cells

Sensitivity to glueocorticoid (GC)-evoked apoptosis in lymphoid cell lines correlates closely with GC-mediated suppression of c-Myc expression. To est ablish a functional role for c-Myc in GC-mediated apoptosis, we have stably expressed MycER (TM), the human c-Myc protein fused to the modified ligand -binding domain of the murine estrogen receptor a, in GC-sensitive CEM-C7-1 4 cells. In CEM-C7-14 cells, MycER (TM) constitutively imparts c-Myc functi ons. Cells expressing MycERT (TM) (C7-MycER (TM)) exhibited a marked reduct ion in cell death after 72 h in 100 nm dexamethasone (Dex), with 10-20-fold more viable cells when compared to the parental CEM-C7-14 clone. General G C responsiveness was not compromised, as evidenced by Dex-mediated suppress ion of endogenous c-Mye and cyclin D3, and induction of c-Jun and the gluco corticoid receptor. MycER (TM) also blunted Dex-mediated upregulation of p2 71(kipI) and suppression of the Myc target p53. In comparison to parental C EM-C7-14 cells, Dex-evoked DNA strand breaks were negligible and caspase ac tivation was delayed, but the extent of GI cell cycle arrest was similar in C7-MycER (TM) cells. Myc-ER (TM) did not result in permanent, complete res istance to GC however, and the GC-treated cells eventually died, indicative of redundant or interactive mechanisms in the GC-evoked lytic response of lymphoid cells. Our results emphasize the importance of c-Myc suppression i n GC-evoked apoptosis of CEM-C7-14 cells.