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

Eur J Cancer. 2005 May;41(7):1086-94. doi: 10.1016/j.ejca.2005.01.018.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Calcium Channel Blockers / pharmacology
  • Cell Line, Tumor
  • Chromosome Aberrations
  • Chromosomes, Human, Pair 7 / genetics
  • Docetaxel
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Genome, Human
  • Humans
  • Nucleic Acid Hybridization
  • Taxoids / therapeutic use*
  • Verapamil / pharmacology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents, Phytogenic
  • Calcium Channel Blockers
  • Taxoids
  • Docetaxel
  • Verapamil