GLUCOCORTICOID-INDUCED GROWTH-INHIBITION AND DIFFERENTIATION OF A HUMAN MEGAKARYOBLASTIC LEUKEMIA-CELL LINE - INVOLVEMENT OF GLUCOCORTICOIDRECEPTOR

A human megakaryoblastic leukemia cell line, HIMeg, was established re cently. Previous studies have shown that retinoic acid (RA) and 1,25-d ihydroxyvitamin D3 [1,25(OH)2 D3] have potent effects on the prolifera tion and differentiation of HIMeg cells. Recently, the effect of dexam ethasone (Dex), a synthetic glucocorticoid, on HIMeg cell growth and d ifferentiation was examined in comparison with RA and sex steroid horm ones. It was observed that in a methylcellulose culture system, Dex su ppressed the clonal proliferation of HIMeg cells in a dose-dependent m anner. The inhibitory effects of Dex could be reversed by RU486, a pot ent glucocorticoid antagonist. In contrast, sex steroid hormones had l ittle effect on the clonal proliferation of HIMeg cells. In a liquid c ulture system, only 2% of HIMeg cells expressed glycoprotein IIb/IIIa (GPIIb/IIIa) antigen without hormone treatment, whereas 45% and 30% of the cells expressed GPIIb/IIIa following the addition of RA and Dex, respectively. To examine the molecular basis of the hormone-induced ce ll differentiation, glucocorticoid receptor (GR) expression was studie d by Scatchard analysis. It was shown that there existed a saturable, high-affinity GR in HIMeg cells and the GR number was altered after De x or RA treatment of the cells, suggesting that the cellular effects o f glucocorticoids on HIMeg cells were mediated by GR.