Regulation of c-kit expression in human myeloid cells.
In both murine and human systems the c-kit ligand, also known as mast cell growth factor (MGF), acts synergistically with several colony stimulating factors, including the granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 3 (IL-3), in stimulating the proliferation and differentiation of different types of hematopoietic progenitors. In addition, MGF is also known to enhance the effects of GM-CSF and IL-3 on the in vitro proliferative activity of myeloid leukemic cells. MGF synergizes with a number of other cytokines such as GM-CSF, IL-3, IL-2, IL-4, IL-6 and IL-9 in sustaining the proliferation of growth factor dependent M-07e cells. In order to explore the molecular basis of this synergistic activity and to elucidate the regulatory mechanisms of c-kit expression, we investigated the effects of GM-CSF, IL-3 and MGF on c-kit mRNA and protein levels in M-07e cells. GM-CSF, unlike MGF and IL-3, induced a transient but significant increase of c-kit mRNA levels. Moreover, following MGF and GM-CSF treatment, c-kit protein expression in M-07e cells decreased, whereas all the other cytokines tested are unable to modulate c-kit protein. These data together with the results of protein turnover analysis suggest that MGF and GM-CSF regulate c-kit expression at the post-transcriptional level. In addition, the finding that IL-3 has no detectable effect on c-kit expression raises the possibility that GM-CSF-induced c-kit regulation is not mediated by the common signal transducing element: the beta subunit of the IL-3/GM-CSF receptor complex.
Brizzi
M F
MF
Dipartimento di Scienze Biomediche e Oncologia Umana, Università di Torino, Italy.
Pavan
M
M
Zini
M G
MG
Avanzi
G C
GC
Pegoraro
L
L
D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007378:Interleukins / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D016184:Receptors, Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D007378:Interleukins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016184:Receptors, Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases