Glucocorticoid-induced growth inhibition and differentiation of a human megakaryoblastic leukemia cell line: involvement of glucocorticoid receptor.

Abstract

A human megakaryoblastic leukemia cell line, HIMeg, was established recently. Previous studies have shown that retinoic acid (RA) and 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3] have potent effects on the proliferation and differentiation of HIMeg cells. Recently, the effect of dexamethasone (Dex), a synthetic glucocorticoid, on HIMeg cell growth and differentiation was examined in comparison with RA and sex steroid hormones. It was observed that in a methylcellulose culture system, Dex suppressed the clonal proliferation of HIMeg cells in a dose-dependent manner. The inhibitory effects of Dex could be reversed by RU486, a potent glucocorticoid antagonist. In contrast, sex steroid hormones had little effect on the clonal proliferation of HIMeg cells. In a liquid culture 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 cell differentiation, glucocorticoid receptor (GR) expression was studied by Scatchard analysis. It was shown that there existed a saturable, high-affinity GR in HIMeg cells and the GR number was altered after Dex or RA treatment of the cells, suggesting that the cellular effects of glucocorticoids on HIMeg cells were mediated by GR.