Regulation of topoisomerase II expression during the VM-26 induced differentiation of IW32 murine erythroleukemia cells.
The effect of VM-26, a topoisomerase II targeting drug, on IW32 murine erythroleukemia cells was investigated. The VM-26 induced IW32 cells to differentiate at a non-toxic but cytostatic concentration (0.01 microgram/ml). More than 40% of the cells were induced to synthesize hemoglobin, and cells were arrested in G2/M phase of the cell cycle. Levels of beta-globin mRNA also increased significantly. Cells became committed to erythroid maturation after 16 h of continuous drug exposure. Replacement with fresh VM-26 after 48 h of drug treatment further increased the hemoglobin containing cells to greater than 80%. Unlike other drug induced erythroleukemia cell differentiation, c-myc mRNA expression was not affected by VM-26. Inhibition of topoisomerase II activity was observed during the first 12 h of VM-26 treatment; however, elevated enzyme activity was found thereafter. Northern blot analysis showed significant increase in the expression of topoisomerase IIalpha mRNA at 12 and 24 h after VM-26 addition. These findings indicate that VM-26 inhibited the activity of topoisomerase II and promoted the committed differentiation of IW32 cells along the erythroid pathway. In addition, a parallel increase in mRNA and activity levels of topoisomerase II in differentiated cells suggests that regulation of the enzyme expression occurred in the VM-26 induced erythroid maturation.
Tan
S K
SK
Faculty of Medical Technology, National Yang-Ming University, Shih-Pai, Taipei, Taiwan.
Tang
S J
SJ
Wang
M C
MC
Hwang
J
J
Wang
F F
FF
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005914:Globins / Q000235:genetics; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013713:Teniposide / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D005914:Globins; D013713:Teniposide; D004250:DNA Topoisomerases, Type II