Drug resistance associated with altered DNA topoisomerase II

Beck, William T.; Danks, Mary K.; Wolverton, Judith S.; Kim, Ryungsa; Chen, Mei

doi:10.1016/0065-2571(93)90012-3

Cited by 79 publications

(66 citation statements)

References 13 publications

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“…This appears modest when compared to the drug resistance in tumour cell lines, which can grow in 20-to 50-fold the amount of drug tolerated by normal cells (reviewed in Beck et al, 1993). Drug-resistant tumour cells usually incur multiple mutations, however, and the resistance is an accumulative effect of mutations in MDR], topoisomerase IIc and perhaps other unknown targets of mutation.…”

Section: Resultsmentioning

confidence: 99%

Ectopic expression of inactive forms of yeast DNA topoisomerase II confers resistance to the anti-tumour drug, etoposide

Vassetzky¹,

Alghisi²,

Roberts³

et al. 1996

Br J Cancer

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Section: Resultsmentioning

confidence: 99%

Ectopic expression of inactive forms of yeast DNA topoisomerase II confers resistance to the anti-tumour drug, etoposide

Vassetzky¹,

Alghisi²,

Roberts³

et al. 1996

Br J Cancer

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“…CD26 and sensitivity to topoisomerase II inhibitors U Aytac et al involvement of other additional factor(s) (Beck et al, 1993;Larsen and Skladanowski, 1998). Furthermore, a functional association between CD26 and topoisomerase II a may also prove to be an important and generalised aspect of CD26 biology.…”

Section: Discussionmentioning

confidence: 99%

Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G2/M arrest induced by topoisomerase II inhibitors

et al. 2003

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CD26/dipeptidyl peptidase IV (DPPIV) is a surface antigen with multiple functions, including a role in T-cell activation and the development of certain human cancers. We previously demonstrated that CD26/DPPIV enhanced sensitivity of Jurkat cells to doxorubicin. We now show that expression of CD26/DPPIV enhanced sensitivity of CD26 Jurkat transfectants to G 2 -M arrest mediated by the antineoplastic agent etoposide. The increased sensitivity to etoposide-induced G 2 -M arrest was associated with disruption of cell cycle-related events, including hyperphosphorylation of p34 cdc2 kinase, change in cdc25C expression and phosphorylation, and alteration in cyclin B1 expression. CD26/DPPIV-associated enhancement of doxorubicin and etoposideinduced G 2 -M arrest was also observed in serum-free media, suggesting an effect of CD26 on cell-derived processes rather than serum-derived factors. Importantly, our work elucidated a potential mechanism for the enhanced susceptibility of CD26-expressing Jurkat cells to the topoisomerase II inhibitors by demonstrating that CD26/DPPIV surface expression was associated with increased topoisomerase II a levels and enhanced enzyme activity. Besides being the first to show a functional association between the multifaceted molecule CD26 and the key cellular protein topoisomerase II a, our studies provide additional evidence of a potential role for CD26 in the treatment of selected malignancies.

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“…We now believe that this is incorrect. All available evidence indicates that non-covalent topoisomerase II poisons act within the active site of the enzyme at the interface between the protein and DNA substrate [15,16,[133][134][135][136][137]. Furthermore, mechanistic studies suggest that it is actually the interactions between topoisomerase II and these compounds that serve as the point of entry into the enzyme-DNA complex [135][136][137][138].…”

Section: Non-covalent Topoisomerase II Poisonsmentioning

confidence: 99%

“…Although topoisomerase II-targeted anticancer drugs act at the enzyme-DNA interface [15,16,104,[133][134][135][136][137], the accumulation of drugs in the double helix has the potential to inhibit enzyme binding or activity. Because the generation of positive superhelical twists by DNA intercalation induces torsional stress in the double helix [130,189], the ability of these molecules to absorb intercalative compounds is limited.…”

Section: Effects Of Dna Supercoiling On Topoisomerase Ii-mediated Dnamentioning

confidence: 99%

DNA topoisomerase II, genotoxicity, and cancer

McClendon

Osheroff

2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

363

466

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Type II topoisomerases are ubiquitous enzymes that play essential roles in a number of fundamental DNA processes. They regulate DNA under-and overwinding, and resolve knots and tangles in the genetic material by passing an intact double helix through a transient double-stranded break that they generate in a separate segment of DNA. Because type II topoisomerases generate DNA strand breaks as a requisite intermediate in their catalytic cycle, they have the potential to fragment the genome every time they function. Thus, while these enzymes are essential to the survival of proliferating cells, they also have significant genotoxic effects. This latter aspect of type II topoisomerase has been exploited for the development of several classes of anticancer drugs that are widely employed for the clinical treatment of human malignancies. However, considerable evidence indicates that these enzymes also trigger specific leukemic chromosomal translocations. In light of the impact, both positive and negative, of type II topoisomerases on human cells, it is important to understand how these enzymes function and how their actions can destablize the genome. This article discusses both aspects of human type II topoisomerases.

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Drug resistance associated with altered DNA topoisomerase II

Cited by 79 publications

References 13 publications

Ectopic expression of inactive forms of yeast DNA topoisomerase II confers resistance to the anti-tumour drug, etoposide

Ectopic expression of inactive forms of yeast DNA topoisomerase II confers resistance to the anti-tumour drug, etoposide

Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G2/M arrest induced by topoisomerase II inhibitors

DNA topoisomerase II, genotoxicity, and cancer

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