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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Detalles Bibliográficos
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
Descripción
Sumario: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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