Genomic changes identified by comparative genomic hybridisation in docetaxel-resistant breast cancer cell lines

Sarah McDonald, David A J Stevenson, Susan Moir, Andrew W. Hutcheon, Neva Elizabeth Haites, Steven Darryll Heys, Andrew Craig Schofield

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. Breast cancers can have an inherent or acquired resistance to docetaxel but the causes of this resistance remain unclear. In this study high-level, docetaxel-resistant human breast cancer cell lines (MCF-7 and MDA-MB-231) were created, and comparative genomic hybridisation was used to identify genomic regions associated with resistance to docetaxel. MCF-7 resistant cells showed an amplification of chromosomes 7q21.11-q22.1, 17q23-q24.3, 18, and deletion of chromosomes 6p, 10q11.2-qter and 12p. MDA-MB-231 resistant cells showed a gain of chromosomes 5p, 7q11.1-q35, 9, and loss of chromosomes 4, 8q24.1-qter, 10, 11q23.1-qter, 12q15-q24.31, 14q and 18. Whole chromosome paints confirmed these findings. Amplification of 7q21 and loss of 10q may represent a common mechanism of acquired docetaxel resistance in breast cancer cells. This study is the first description of a genomic approach specifically to identify genomic regions involved in resistance to docetaxel.
Original languageEnglish
Pages (from-to)1086-94
Number of pages9
JournalEuropean Journal of Cancer
Volume41
Issue number7
Early online date7 Apr 2005
DOIs
Publication statusPublished - 1 May 2005

Keywords

  • Antineoplastic Agents, Phytogenic
  • Breast Neoplasms
  • Calcium Channel Blockers
  • Cell Line, Tumor
  • Chromosome Aberrations
  • Chromosomes, Human, Pair 7
  • Drug Resistance, Neoplasm
  • Female
  • Genome, Human
  • Humans
  • Nucleic Acid Hybridization
  • P-Glycoprotein
  • Taxoids
  • Verapamil
  • breast neoplasms
  • chromosome aberrations
  • In situ hybridisation fluorescence
  • taxoids
  • anti-neoplastic agents
  • drug therapy
  • Drug resistance

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