Stem Cells, Vol 11, 312-318, Copyright © 1993 by AlphaMed Press
Glucocorticoid-induced growth inhibition and differentiation of a human megakaryoblastic leukemia cell line: involvement of glucocorticoid receptor
LN Song and T Cheng
Department of Pathophysiology, Second Military Medical University, Shanghai, China.
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.
