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

• Published in: Oncogene Vol. 8; no. 4; p. 933
• Main Authors: Smith, K, Houlbrook, S, Greenall, M, Carmichael, J, Harris, A L
• Format: Journal Article
• Language: English
• Published: England 01-04-1993
• Subjects: Adult; Aged; Amsacrine - pharmacology; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; DNA Topoisomerases, Type II - genetics; DNA, Neoplasm - genetics; Gene Amplification; Humans; In Vitro Techniques; Lymphatic Metastasis; Middle Aged; Mitoxantrone - pharmacology; Oncogenes; Proto-Oncogene Proteins - genetics; Receptor, Epidermal Growth Factor - metabolism; Receptor, ErbB-2; Receptors, Estrogen - metabolism; Tumor Cells, Cultured
• ISSN: 0950-9232

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.