Analysis of granulocyte-macrophage colony-stimulating factor action in differentiating myeloid leukemia cells: treatment with DMSO may reveal a common pathway for growth factor gene regulation.
Previous studies showed that factor-independent, late-passage HL60 acute nonlymphocytic leukemia (ANLL) cells proliferated in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) after treatment with dimethylsulfoxide (DMSO) or other agents inducing cellular differentiation. In the present studies, we examined mechanisms of this response. After treatment with DMSO, GM-CSF delayed expression of some HL60 differentiation programs (CD11b expression), but not others (nitro blue tetrazolium dye reduction), and delayed the exit of cells from the cell cycle. In the presence of DMSO, GM-CSF but not granulocyte colony-stimulating factor (G-CSF) increased expression of steady-state c-myc RNA. DMSO-treated HL60 cells expressing heterologous epidermal growth factor (EGF) receptors also proliferated in response to EGF and showed increased c-myc expression. Nuclear transcription studies showed that GM-CSF did not alter c-myc transcription in DMSO-treated cells, and studies using actinomycin-D showed no increase in steady-state c-myc RNA half-life. These studies indicate that GM-CSF increases post-deterministic proliferation and alters the phenotype of differentiating HL60 cells, and post-transcriptional alterations in c-myc expression may be responsible for some of these changes. Heterologous EGF receptors mediate similar responses, suggesting that treating HL60 cells with DMSO may reveal a common pathway of growth factor gene regulation.
Taetle
R
R
Division of Hematology/Oncology, University of California San Diego Cancer Center.
Oval
J
J
Smedsrud
M
M
Davis
C
C
Gansbacher
B
B
D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003609:Dactinomycin / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000502:physiology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D016271:Proto-Oncogene Proteins c-myc; D003609:Dactinomycin; D004815:Epidermal Growth Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D066246:ErbB Receptors; D004121:Dimethyl Sulfoxide