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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.

Type

Journal article

Journal

Oncogene

Publication Date

04/1993

Volume

8

Pages

933 - 938

Keywords

Adult, Aged, Amsacrine, Breast Neoplasms, DNA Topoisomerases, Type II, DNA, Neoplasm, ErbB Receptors, Gene Amplification, Humans, In Vitro Techniques, Lymphatic Metastasis, Middle Aged, Mitoxantrone, Oncogenes, Proto-Oncogene Proteins, Receptor, ErbB-2, Receptors, Estrogen, Tumor Cells, Cultured