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- W269738581 abstract "Resistance to chemotherapeutic agents can arise in genetically unstable cultured cell lines as a result of amplifications of specific genes, such as those coding for drug efflux proteins or critical enzymes. In the clinical setting, resistance mechanisms are less well understood. In addition to the multi-drug resistance phenotype attributable to overexpression of P-glycoprotein encoded by the MDR1 gene, other resistance mechanisms may also be involved. We have attempted to identify genes associated with resistance to common chemotherapeutic agents by screening drug resistant cell lines for presence of DNA amplifications by comparative genomic hybridization. Hybridizations with DNA from a drug-resistant cell line against the drug-sensitive parental allowed us to rapidly identify differences between two-genetically highly complex specimens. Experiments were carried out using MCF-7 breast cancer, WiDr colorectal cancer, and 8226 human myeloma cell lines that had been selected for resistance against doxorubicine, mitroxantrone or melphalan. None of the mitoxantrone-resistant cell lines showed evidence of DNA amplification. In contrast, cell lines selected with doxorubicine as well as those subsequently selected with melphalan showed a large number of amplifications affecting several different chromosomal sites. These involved both known drug-resistance gene loci, 7p12-q21 (MDR1 gene) and 16p (MRP gene), as well as regions thatmore » have not previously been implicated in drug resistance, such as 1p22-p33, 6q21-q24, 12p11-pter, 14q13-q22, and 18p. In conclusion, several amplification sites associated with in vitro resistance to chemotherapeutic agents were found. This suggests that the genetic mechanisms underlying resistance development may be complex. It will be important to determine which of these sites harbor actual drug-resistance genes and which are only co-amplified along with an important resistance gene.« less" @default.
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- W269738581 date "1994-09-01" @default.
- W269738581 modified "2023-09-28" @default.
- W269738581 title "Mapping gene amplifications arising during acquisition of drug resistance in cultured cell lines by comparative genomic hybridization" @default.
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