The combination of Steel factor and GM-CSF blocks apoptosis induced by retinoic acid and upregulates AP-1 in a human growth factor-dependent cell line.
The effects of hematopoietic growth factors were examined on the cellular action of retinoic acid (RA) using the human factor-dependent cell line, MO7e. Treatment of cells with Steel factor (SLF) plus granulocyte-macrophage colony-stimulating factor (GM-CSF) synergistically stimulated cell proliferation compared to that with each factor alone. This synergism was even greater in the presence of RA than in its absence. Treatment of cells with RA resulted in apoptotic cell death associated with internucleosomal DNA fragmentation in the presence of either SLF or GM-CSF. RA-induced apoptosis and DNA fragmentation were completely blocked by treating cells with SLF plus GM-CSF. Northern analysis showed that the inhibition of RA effects on MO7e cells by SLF plus GM-CSF treatment occurred without modulation of expression of RA receptor-alpha (RAR-alpha) gene. Furthermore, a higher amount of AP-1 complex was detected by electrophoretic mobility shift assays in a nuclear extract prepared from cells treated with SLF plus GM-CSF compared to those treated with each factor alone, while the level of RAR-complex remained similar in cells treated with SLF and/or GM-CSF. These data suggest an interaction in signaling pathways among different types of receptors that might be associated with the AP-1 complex.
Horie
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Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis 46202-5121.
Broxmeyer
H E
HE
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D016298:Hematopoietic Cell Growth Factors / Q000502:physiology*; D006801:Humans; D019089:Stem Cell Factor; D018808:Transcription Factor AP-1 / Q000096:biosynthesis*; D014212:Tretinoin / Q000037:antagonists & inhibitors*; D015854:Up-Regulation
D016298:Hematopoietic Cell Growth Factors; D019089:Stem Cell Factor; D018808:Transcription Factor AP-1; D014212:Tretinoin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor