Expression and functional role of the proto-oncogene c-kit in acute myeloblastic leukemia cells.
The c-kit proto-oncogene encodes a receptor tyrosine kinase that is thought to play an important role in hematopoiesis. In a series of human acute myeloblastic leukemia (AML), the expression of the c-kit proto-oncogene and its product was studied by means of Northern blot and immunoblot analyses. The c-kit mRNA was expressed in 20 of 25 cases of AML, and in those cases the product of the c-kit proto-oncogene was detected by immunoblotting with anti-c-kit antibody. The expression of c-kit transcripts and protein was barely detectable in normal bone marrow cells as a control. The expression of c-kit transcript did not correlate with the French-American-British classification nor clinical manifestations. In 6 of 11 cases that expressed c-kit product, AML cells were found to proliferate in response to recombinant human stem cell factor (rhSCF), the ligand for c-kit, and the synergistic stimulation of AML cells was observed by rhSCF and granulocyte-macrophage colony-stimulating factor. Immunoblotting with anti-phosphotyrosine antibody showed that the c-kit receptor protein was detectably phosphorylated in 7 of 12 cases tested before the stimulation with rhSCF, while the rhSCF treatment resulted in an increased tyrosine phosphorylation of c-kit in AML cells. These results indicate that c-kit proto-oncogene is expressed in most cases of AML and is functional in terms of supporting proliferation.
Ikeda
H
H
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Kanakura
Y
Y
Tamaki
T
T
Kuriu
A
A
Kitayama
H
H
Ishikawa
J
J
Kanayama
Y
Y
Yonezawa
T
T
Tarui
S
S
Griffin
J D
JD
D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division; D015870:Gene Expression; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation; D019000:Phosphotyrosine; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D016298:Hematopoietic Cell Growth Factors; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D019000:Phosphotyrosine; D014443:Tyrosine; D019009:Proto-Oncogene Proteins c-kit