Inhibition of erythroid differentiation by stem cell factor in K562 cells expressing the c-kit gene.
We found a K562 subclone (K562YO) that highly expressed the c-kit gene. K562YO had a higher capability of erythroid differentiation by hemin and cytosine arabinoside (Ara-C) than its parent K562 (KIT-). We obtained the transfectant expressing c-kit by introducing c-kit cDNA into K562 (KIT-). The differentiation of the transfectant was similar to that of the parent cell. Thus the difference described above was not due to the expression of c-kit. Next, we investigated the effects of stem cell factor (SCF) on the differentiation of the K562 cell expressing c-kit. SCF did not enhance the cell growth of K562YO. On the other hand, SCF suppressed induction of benzidine-positive cells when c-kit-positive cells were treated with hemin and Ara-C, especially at a low concentration. Furthermore, c-kit mRNA and protein were down-regulated during erythroid differentiation. SCF also downregulated the c-kit proteins. Our results suggest that the SCF/c-kit signals could act negatively for erythroid differentiation of the K562 cells expressing c-kit. K562YO is also useful for studying the mechanism that controls the expression of the c-kit gene because there is a K562 counterpart cell line that does not express this gene.
Ogawa
K
K
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Tashima
M
M
Toi
T
T
Sawai
H
H
Sawada
H
H
Fujita
J
J
Maruyama
Y
Y
Okuma
M
M
D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003561:Cytarabine / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000235:genetics; D015672:Erythroid Precursor Cells / Q000737:chemistry / Q000473:pathology* / Q000502:physiology; D004920:Erythropoiesis / Q000502:physiology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016298:Hematopoietic Cell Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D010766:Phosphorylation; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit; D011519:Proto-Oncogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D016184:Receptors, Colony-Stimulating Factor / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D019089:Stem Cell Factor; D014162:Transfection; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D004273:DNA, Neoplasm; D016298:Hematopoietic Cell Growth Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016184:Receptors, Colony-Stimulating Factor; D019089:Stem Cell Factor; D003561:Cytarabine; D014443:Tyrosine; D006427:Hemin; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases