Modulation of human G-CSF receptor mRNA and protein in normal and leukemic myeloid cells by G-CSF and retinoic acid.
Granulocyte colony-stimulating factor (G-CSF) is produced by several cell types throughout the body and has a variety of effects on neutrophils and their precursors, which are mediated by binding to its receptor. It is not yet known what physiologic factors modulate G-CSF receptor mRNA expression in these cells. We studied the effect of G-CSF on freshly isolated neutrophils and bone marrow cells from normal human subjects and on myeloid leukemic cell lines. We found that G-CSF receptor mRNA levels were maintained by G-CSF in neutrophils but not in bone marrow cells. Of the leukemic cell lines tested, K562 and BV173, both of which contain the bcr-abl translocation, neither expressed G-CSF receptor mRNA. Whereas G-CSF did not affect mRNA levels for its receptor in myeloid leukemic cell lines, exposure of the acute promyelocytic cell line, NB4, to all-trans retinoic acid induced a striking increase in G-CSF receptor mRNA expression and resulted in increased G-CSF receptor surface expression. The effect of retinoic acid on G-CSF receptor mRNA on NB4 cells occurred early, before morphologic evidence of differentiation, and required protein synthesis. All-trans retinoic acid also upregulated G-CSF receptor mRNA in the myeloid leukemia cell line HL-60. Thus, maintenance of G-CSF receptor on neutrophils by G-CSF may extend the duration of ligand responsiveness. Furthermore, the ability of retinoic acid to up-regulate G-CSF receptor may account for the synergistic effect of G-CSF and retinoic acid in differentiation induction of acute promyelocytic leukemia.
Tkatch
L S
LS
Department of Medicine, University of Pittsburgh School of Medicine, PA, USA.
Rubin
K A
KA
Ziegler
S F
SF
Tweardy
D J
DJ
D005786:Gene Expression Regulation / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000032:analysis / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; D014212:Tretinoin