Ectopic cyclin D1 expression blocks STI571-induced erythroid differentiation of K562 cells

Takeshi Kawano; Junko Horiguchi-Yamada; Shinobu Saito; Satsuki Iwase; Yusuke Furukawa; Yasuhiko Kano; Hisashi Yamada

doi:10.1016/j.leukres.2003.10.022

Ectopic cyclin D1 expression blocks STI571-induced erythroid differentiation of K562 cells

Leuk Res. 2004 Jun;28(6):623-9. doi: 10.1016/j.leukres.2003.10.022.

Authors

Takeshi Kawano¹, Junko Horiguchi-Yamada, Shinobu Saito, Satsuki Iwase, Yusuke Furukawa, Yasuhiko Kano, Hisashi Yamada

Affiliation

¹ Department of Molecular Genetics, Institute of DNA Medicine, Jikei University School of Medicine, Nishi-Shinbashi 3-25-8, Minato-ku, Tokyo 105-8461, Japan.

PMID: 15120940
DOI: 10.1016/j.leukres.2003.10.022

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Benzamides
Benzoquinones
Cell Differentiation / drug effects*
Cyclin D1 / metabolism*
Down-Regulation
Drug Resistance, Neoplasm
Enzyme Inhibitors / pharmacology*
Erythroid Precursor Cells / drug effects*
Erythroid Precursor Cells / pathology
Glycophorins / metabolism
Humans
Imatinib Mesylate
K562 Cells
Lactams, Macrocyclic
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase Kinases / metabolism
Mitogen-Activated Protein Kinases / metabolism
Phosphorylation
Piperazines / pharmacology*
Protein-Tyrosine Kinases / antagonists & inhibitors
Pyrimidines / pharmacology*
Quinones / pharmacology
Rifabutin / analogs & derivatives
Signal Transduction
Transfection

Substances

Benzamides
Benzoquinones
Enzyme Inhibitors
Glycophorins
Lactams, Macrocyclic
Piperazines
Pyrimidines
Quinones
Cyclin D1
Rifabutin
herbimycin
Imatinib Mesylate
Protein-Tyrosine Kinases
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase Kinases