Topoisomerase II alpha co-amplification with erbB2 in human primary breast cancer and breast cancer cell lines: relationship to m-AMSA and mitoxantrone sensitivity

Oncogene. 1993 Apr;8(4):933-8.


Topoisomerase II alpha (topo II alpha) is a key enzyme in DNA replication and a target for many anti-cancer drugs. High levels are associated with sensitivity to topoisomerase II inhibitors. Because its chromosome location is similar to erbB2 (17q21-22), which is frequently amplified in breast cancer, co-amplification of these genes was assessed. In 117 primary breast cancers, 25 were amplified for erbB2. Three of these cases showed co-amplification of topo II alpha. Topo II beta was not amplified. Four human breast cancer cell lines were assessed for erbB2 and topo II alpha co-amplification. They were also analysed for sensitivity to the topoisomerase inhibitors m-AMSA and mitoxantrone. The most sensitive cell line was SKBr3, which was the only one with erbB2 amplification. Topo II alpha was co-amplified to a similar extent as in tumours. This suggests that patients whose tumours show topo II alpha amplification should be assessed specifically for therapy with topoisomerase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amsacrine / pharmacology
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • DNA Topoisomerases, Type II / genetics*
  • DNA, Neoplasm / genetics
  • ErbB Receptors / metabolism
  • Gene Amplification*
  • Humans
  • In Vitro Techniques
  • Lymphatic Metastasis
  • Middle Aged
  • Mitoxantrone / pharmacology
  • Oncogenes*
  • Proto-Oncogene Proteins / genetics*
  • Receptor, ErbB-2
  • Receptors, Estrogen / metabolism
  • Tumor Cells, Cultured


  • DNA, Neoplasm
  • Proto-Oncogene Proteins
  • Receptors, Estrogen
  • Amsacrine
  • Mitoxantrone
  • ErbB Receptors
  • Receptor, ErbB-2
  • DNA Topoisomerases, Type II