Response to ICRF-159 in cell lines resistant to cleavable complex-forming topoisomerase II inhibitors.

We have studied the relationship between expression of genes implicated in mediating resistance to cleavable complex-forming topoisomerase II (topo II) inhibitors and cellular sensitivity to ICRF-159, a 'catalytic' inhibitor of topo II. Overexpression of the membrane transporters, P-glycop...

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Autores principales: Davies, S. L., Bergh, J., Harris, A. L., Hickson, I. D.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group|1 1997
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063389/
https://www.ncbi.nlm.nih.gov/pubmed/9062401
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author Davies, S. L.
Bergh, J.
Harris, A. L.
Hickson, I. D.
author_facet Davies, S. L.
Bergh, J.
Harris, A. L.
Hickson, I. D.
author_sort Davies, S. L.
collection PubMed
description We have studied the relationship between expression of genes implicated in mediating resistance to cleavable complex-forming topoisomerase II (topo II) inhibitors and cellular sensitivity to ICRF-159, a 'catalytic' inhibitor of topo II. Overexpression of the membrane transporters, P-glycoprotein and multidrug resistance-related protein (MRP), or down-regulation of topo IIalpha and/or -beta, did not confer ICRF-159 resistance. Indeed, marked topo IIalpha down-regulation appeared to be associated with collateral sensitivity to ICRF-159. Our results indicate that the resistance mechanisms that pertain to cleavable complex-forming topo II inhibitors and ICRF-159 are distinct. The evidence presented here suggests that topo IIalpha, not topo IIbeta, is more likely to be the major in vivo target for ICRF-159. IMAGES:
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spelling pubmed-20633892009-09-10 Response to ICRF-159 in cell lines resistant to cleavable complex-forming topoisomerase II inhibitors. Davies, S. L. Bergh, J. Harris, A. L. Hickson, I. D. Br J Cancer Research Article We have studied the relationship between expression of genes implicated in mediating resistance to cleavable complex-forming topoisomerase II (topo II) inhibitors and cellular sensitivity to ICRF-159, a 'catalytic' inhibitor of topo II. Overexpression of the membrane transporters, P-glycoprotein and multidrug resistance-related protein (MRP), or down-regulation of topo IIalpha and/or -beta, did not confer ICRF-159 resistance. Indeed, marked topo IIalpha down-regulation appeared to be associated with collateral sensitivity to ICRF-159. Our results indicate that the resistance mechanisms that pertain to cleavable complex-forming topo II inhibitors and ICRF-159 are distinct. The evidence presented here suggests that topo IIalpha, not topo IIbeta, is more likely to be the major in vivo target for ICRF-159. IMAGES: Nature Publishing Group|1 1997 /pmc/articles/PMC2063389/ /pubmed/9062401 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
Davies, S. L.
Bergh, J.
Harris, A. L.
Hickson, I. D.
Response to ICRF-159 in cell lines resistant to cleavable complex-forming topoisomerase II inhibitors.
title Response to ICRF-159 in cell lines resistant to cleavable complex-forming topoisomerase II inhibitors.
title_full Response to ICRF-159 in cell lines resistant to cleavable complex-forming topoisomerase II inhibitors.
title_fullStr Response to ICRF-159 in cell lines resistant to cleavable complex-forming topoisomerase II inhibitors.
title_full_unstemmed Response to ICRF-159 in cell lines resistant to cleavable complex-forming topoisomerase II inhibitors.
title_short Response to ICRF-159 in cell lines resistant to cleavable complex-forming topoisomerase II inhibitors.
title_sort response to icrf-159 in cell lines resistant to cleavable complex-forming topoisomerase ii inhibitors.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063389/
https://www.ncbi.nlm.nih.gov/pubmed/9062401
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