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Regulation of the differentiation of WEHI-3B D+ leukemia cells by granulocyte colony-stimulating factor receptor.
Li, J; Koay, D C; Xiao, H; Sartorelli, A C.
Afiliación
  • Li J; Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
J Cell Biol ; 120(6): 1481-9, 1993 Mar.
Article en En | MEDLINE | ID: mdl-7680656
ABSTRACT
To investigate the role of the G-CSF receptor (G-CSFR) in mediating the action of G-CSF, WEHI-3B D+ murine myelomonocytic leukemia cells were transfected with a plasmid containing the murine G-CSFR gene. Overexpression of G-CSFR in transfected clones was demonstrated by northern blotting, binding of [125I]rhG-CSF and cross-linking experiments. A high level of expression of the G-CSFR did not promote or suppress cellular proliferation or initiate differentiation; however, exposure of transfected cells to G-CSF in suspension culture caused a large percentage of the population to enter a differentiation pathway, as determined by two markers of the mature state, the ability of cells to reduce nitroblue tetrazolium (NBT) and to express the differentiation antigen Mac-1 (CD11b) on the cell surface. Thus, upon treatment with 10 ng/ml of G-CSF, 60% or more of transfected cells exhibited NBT positivity; whereas, in contrast, nontransfected cells exhibited only 6% NBT positivity in response to G-CSF. An eightfold increase in Mac-1 expression over that of the parental line was also observed in transfected cells exposed to G-CSF. The growth rate of the transfected clones was decreased by exposure to G-CSF, presumably due to terminal differentiation. The findings suggest that the predominant function of G-CSF and its receptor in WEHI-3B D+ cells is to mediate differentiation and that the level of the G-CSFR portion of the signal transduction mechanism in this malignant cell line is important for a response to the maturation inducing function of the cytokine.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Diferenciación Celular / Receptores de Factor Estimulante de Colonias de Granulocito Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Cell Biol Año: 1993 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Diferenciación Celular / Receptores de Factor Estimulante de Colonias de Granulocito Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Cell Biol Año: 1993 Tipo del documento: Article