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Published on: January 7, 2019
A DNA uptake-stimulating protein increases the antiproliferative effect of c-myb antisense oligonucleotide on
György Tóth1, József Schlammadinger, János Aradi
1Department of Human Genetics, University of Debrecen, Medical and Health Science Center, Faculty of Medicine, Debrecen, Hungary.
Abstract:
Proliferation of HL-60 and MOLT4 leukemia cells was inhibited by a c-myb antisense oligonucleotide (ASO) in the presence of a DNA uptake-stimulating protein (DNA uptake-stimulating factor, DUSF). The inhibitory effect was very mild in the absence of DUSF. Sense oligonucleotides or DUSF, alone or in combination, were found to be ineffective. Cellular expression of the c-myb protein was significantly more inhibited by the c-myb ASO in the presence than in the absence of DUSF. In the presence of DUSF, c-myb protein practically disappeared from the nuclei of HL-60 and MOLT4 cells treated with the ASO. Thus, DUSF appears to effectively stimulate the uptake of c-myb ASO into tumor cells in vitro, augmenting its antiproliferative effect by decreasing c-myb expression.
Insights
A DNA uptake-stimulating factor (DUSF) enhances the antiproliferative effect of c-myb antisense oligonucleotide (ASO) in leukemia cells. DUSF boosts ASO uptake, significantly reducing c-myb protein expression and cell proliferation.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Antisense oligonucleotides (ASOs) offer targeted therapeutic potential for cancer by inhibiting specific gene expression.
- The efficacy of ASOs can be limited by cellular uptake efficiency.
- The c-myb proto-oncogene is implicated in the proliferation of various leukemia cell lines.
Purpose of the Study:
- To investigate the role of a DNA uptake-stimulating factor (DUSF) in enhancing the antiproliferative activity of c-myb antisense oligonucleotides (ASOs).
- To determine if DUSF improves the cellular uptake and subsequent inhibition of c-myb protein expression by ASOs in leukemia cells.
Main Methods:
- Treatment of HL-60 and MOLT4 leukemia cells with c-myb ASO in the presence or absence of DUSF.
- Assessment of cell proliferation inhibition.
- Quantification of cellular c-myb protein expression levels, particularly in the nucleus.
Main Results:
- c-myb ASO significantly inhibited proliferation of HL-60 and MOLT4 cells only when DUSF was present; the effect was mild without DUSF.
- DUSF alone, sense oligonucleotides, or the combination of sense oligonucleotides and DUSF showed no inhibitory effect.
- Cellular c-myb protein expression was markedly reduced by c-myb ASO in the presence of DUSF, with near-complete disappearance from nuclei.
Conclusions:
- DUSF effectively stimulates the in vitro uptake of c-myb ASO into leukemia cells.
- DUSF augments the antiproliferative effect of c-myb ASO by enhancing its ability to decrease c-myb expression.
- This study highlights DUSF as a potential enhancer for ASO-mediated cancer therapy.
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