Mitogen-induced topoisomerase II synthesis precedes DNA synthesis in human breast cancer cells.
Cells released from quiescence exhibit increased levels of the DNA-modifying enzyme topoisomerase II, a nuclear protein which is also a target for antitumour drugs such as VP-16 (etoposide) and m-AMSA (4',9'-acridinylamino-methanesulfon-m-anisidide). By using Western blotting, DNA-protein crosslinking and drug-induced DNA cleavage to detect topoisomerase II, we show here that oestrogen stimulation of T-47D human breast cancer cells results in increased cellular enzyme content at least 4hr prior to enhancement of DNA synthesis. Taken in conjunction with previous findings, these results suggest that oestrogen enhances topoisomerase II synthesis within a G1-phase cell subset.
Epstein
R J
RJ
Department of Clinical Oncology & Radiotherapeutics, MRC Centre, Cambridge, U.K.
Smith
P J
PJ
D000677:Amsacrine / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D003432:Cross-Linking Reagents; D004247:DNA; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis*; D004273:DNA, Neoplasm / Q000096:biosynthesis* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D014407:Tumor Cells, Cultured
D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; D004967:Estrogens; D000677:Amsacrine; D005047:Etoposide; D004247:DNA; D004250:DNA Topoisomerases, Type II