Topoisomerase II alpha co-amplification with erbB2 in human primary breast cancer and breast cancer cell lines: relationship to m-AMSA and mitoxantrone sensitivity.
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.
Smith
K
K
Molecular Oncology Laboratories, Imperial Cancer Research Fund, University of Oxford, UK.
Houlbrook
S
S
Greenall
M
M
Carmichael
J
J
Harris
A L
AL
D000328:Adult; D000368:Aged; D000677:Amsacrine / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism; D005784:Gene Amplification; D006801:Humans; D066298:In Vitro Techniques; D008207:Lymphatic Metastasis; D008875:Middle Aged; D008942:Mitoxantrone / Q000494:pharmacology; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000677:Amsacrine; D004250:DNA Topoisomerases, Type II; D004273:DNA, Neoplasm; D066246:ErbB Receptors; D008942:Mitoxantrone; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen