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Regulation of topoisomerase II expression during the VM-26 induced differentiation of IW32 murine erythroleukemia cells.

Abstract：

: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.

journal_name

Leuk Res

journal_title

Leukemia research

authors

Tan SK,Tang SJ,Wang MC,Hwang J,Wang FF

doi

10.1016/0145-2126(95)00144-1

subject

Has Abstract

pub_date

1996-03-01 00:00:00

pages

249-57

issue

3

eissn

0145-2126

issn

1873-5835

pii

0145-2126(95)00144-1

journal_volume

20

pub_type

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