Ectopic cyclin D1 expression blocks STI571-induced erythroid differentiation of K562 cells.
Bcr-Abl tyrosine kinase inhibitor induces apoptosis and erythroid differentiation of K562 cells. During this erythroid differentiation, c-Myc and cyclin D1 transcripts are transiently downregulated. Accordingly, we studied the effect of cyclin D1 overexpression on erythroid differentiation. After treatment with 250 nM STI571, 90% of K562 and 25% of K562/D1 cells underwent erythroid differentiation. The basal expression of glycophorin A in K562/D1 cells was markedly diminished compared with that by parental cells. STI571 treatment failed to induce glycophorin A expression in K562/D1 cells. During STI571 treatment, ERK activity was downregulated in parental cells, while it was constantly activated in K562/D1 cells. These results suggest that ectopic expression of cyclin D1 causes the resistance of K562 cells to erythroid differentiation by modulating ERK regulation.
Kawano
Takeshi
T
Department of Molecular Genetics, Institute of DNA Medicine, Jikei University School of Medicine, Nishi-Shinbashi 3-25-8, Minato-ku, Tokyo 105-8461, Japan.
Horiguchi-Yamada
Junko
J
Saito
Shinobu
S
Iwase
Satsuki
S
Furukawa
Yusuke
Y
Kano
Yasuhiko
Y
Yamada
Hisashi
H
D001549:Benzamides; D016227:Benzoquinones; D002454:Cell Differentiation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000473:pathology; D006021:Glycophorins / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D047029:Lactams, Macrocyclic; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D014162:Transfection
D001549:Benzamides; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D006021:Glycophorins; D047029:Lactams, Macrocyclic; D010879:Piperazines; D011743:Pyrimidines; D011809:Quinones; D019938:Cyclin D1; D017828:Rifabutin; C020754:herbimycin; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases