Chromosome microdissection identifies genomic amplifications associated with drug resistance in a leukemia cell line: an approach to understanding drug resistance in cancer

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• 作者：Frouzandeh Mahjoubi ; Ronald J. Hill and Greg B. Peters
• 关键词：chromosome microdissection ; drug resistance ; leukemia ; MDR ; MRP
• 刊名：Chromosome Research
• 出版年：2006
• 出版时间：April 2006
• 年：2006
• 卷：14
• 期：3
• 页码：263-276
• 全文大小：372 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Human Genetics
  Animal Genetics and Genomics
  Plant Genetics and Genomics
  
• 出版者：Springer Netherlands
• ISSN：1573-6849

文摘

A significant problem encountered in the treatment of cancer patients is that cancer cells often evolve resistance to chemotherapeutic agents. One of the mechanisms responsible for drug resistance is gene amplification. The study of the behavior of genes conferring drug resistance is very important to determine future treatments for cancer patients that will minimize the effect of gene amplification. One of the best methods to investigate this phenomenon is to use chromosome microdissection to directly access the amplified gene or genes. In the present study, chromosome microdissection and fluorescent in-situ hybridization (FISH) were applied for the identification of genes residing in a homogeneously staining region (HSR) in drug-resistant cell sublines developed by treatment of the T-cell leukemia cell line CCRF-CEM with increasing levels of the anthracycline, epirubicin. We have demonstrated that the selection by epirubicin actually elevated the level of the multidrug resistance-associated protein (MRP1) gene. We argue that the breakage fusion bridge (B-F-B) cycle offers a plausible explanation for this amplification. The DNA prepared from the amplified regions by chromosome microdissection provides a resource for future investigations looking for the possible presence of novel genes contributing to drug resistance.