Thulasi R, Harbour D V, Thompson E B
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555-0645.
J Biol Chem. 1993 Aug 25;268(24):18306-12.
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.
糖皮质激素可引起克隆化的人白血病CEM - C7细胞发生细胞溶解。仅在同时具有糖皮质激素受体和完整溶解功能的CEM克隆中，地塞米松对c - myc mRNA的抑制作用才与细胞溶解密切相关。我们通过在存在地塞米松的情况下阻止c - myc基因的下调以及用反义寡核苷酸降低c - myc mRNA水平，来检验c - myc抑制对于糖皮质激素诱导的淋巴细胞溶解至关重要这一理论。我们发现，c - myc的持续表达可使细胞对地塞米松诱导的溶解产生抗性，而反义c - myc寡聚物可诱导细胞溶解。地塞米松对这些白血病细胞的致死作用似乎涉及将c - myc降低至维持细胞生长和完整性所需水平以下。
