Constitutive expression of exogenous c-myb gene causes maturation block in monocyte-macrophage differentiation.
A nuclear protooncogene c-myb has been hypothesized to play an important role in hematopoiesis, but little is known about the physiological function of the c-myb gene products. To study the role of c-myb gene expression in monocyte-macrophage differentiation and proliferation, we introduced exogenous c-myb gene into murine myelomonocytic leukemia WEHI-3B(D+) cells which can be induced to differentiate into mature monocytes with granulocyte-colony stimulation factor (G-CSF) and actinomycin D. Expression of the transfected gene was found to result in elevated levels of c-myb transcripts, which were not subject to normal down-regulation by differentiation induction. This constitutive expression of c-myb gene allowed the c-myb transfectants to differentiate into promonocytes with G-CSF and actinomycin D, but blocked further maturation from promonocytes to mature monocytes. It is concluded that normal down-regulation of c-myb gene expression during monocyte-macrophage differentiation is required for the maturation of promonocytes to mature monocytes.
Yanagisawa
H
H
Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Nagasawa
T
T
Kuramochi
S
S
Abe
T
T
Ikawa
Y
Y
Todokoro
K
K
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004247:DNA / Q000235:genetics; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D009000:Monocytes / Q000166:cytology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb; D012313:RNA / Q000032:analysis; D014162:Transfection; D014407:Tumor Cells, Cultured
D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D016179:Granulocyte Colony-Stimulating Factor; D003609:Dactinomycin; D012313:RNA; D004247:DNA; D011505:Protein-Tyrosine Kinases