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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.

Original publication

DOI

10.1038/bjc.1997.146

Type

Journal article

Journal

Br J Cancer

Publication Date

1997

Volume

75

Pages

816 - 821

Keywords

Antineoplastic Agents, Breast Neoplasms, DNA Topoisomerases, Type II, Down-Regulation, Drug Resistance, Neoplasm, Humans, Male, RNA, Messenger, Razoxane, Testicular Neoplasms, Topoisomerase II Inhibitors, Tumor Cells, Cultured