Isolation of genetic suppressor elements, inducing resistance to topoisomerase II-interactive cytotoxic drugs, from human topoisomerase II cDNA.

摘要: Abstract Many cytotoxic anticancer drugs act at topoisomerase II (topo II) by stabilizing cleavable complexes with DNA formed this enzyme. Several cell lines, selected for resistance to topo II-interactive drugs, show decreased expression or activity of II, suggesting that such a decrease may be responsible drug resistance. In the present study, etoposide was used as selection strategy isolate genetic suppressor elements (GSEs) from retroviral library expressing random fragments human (alpha form) cDNA. Twelve GSEs were isolated, encoding either peptides corresponding short segments alpha molecule (2.4-6.5% protein) 163- 220-bp-long antisense RNA sequences. Expression GSE led cellular protein. Both types induced several poisons but not do II. These results provide direct evidence inhibition in indicate structural domains capable independent functional interactions, and demonstrate constitutes an efficient approach generation mammalian cells.