Hormone and cytotoxic drug responsiveness of cultured human breast cancer cells resistant to specific hormones.
Attempts have been made to develop sublines of MCF-7 cells resistant to the growth-inhibitory actions of medroxyprogesterone acetate (MPA), dexamethasone (DEX), anti-oestrogens or high-dose oestradiol (E2) by prolonged exposure to high hormone concentrations. While high degrees of resistance to MPA, DEX and E2 were achieved, cells remained anti-oestrogen-sensitive after prolonged treatment with 4 microM tamoxifen (TAM) or the anti-oestrogen LY 117018 (LY). Cells resistant to DEX were also resistant to MPA, while cells resistant to high-dose E2 remained sensitive to TAM. Cells resistant to MPA and E2 appeared to be less responsive to cytotoxic drugs than wild-type cells, while resistance to DEX was associated with increased sensitivity. The responses of tumours to cytotoxic drugs may be affected by prior endocrine therapy.
Coldham
N G
NG
Department of Chemical Pathology, St. Mary's Hospital Medical School, London, UK.
Patel
K
K
Braunsberg
H
H
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004351:Drug Resistance; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D008525:Medroxyprogesterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D008727:Methotrexate / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014750:Vincristine / Q000494:pharmacology*
D011759:Pyrrolidines; D013876:Thiophenes; D013629:Tamoxifen; D004958:Estradiol; D014750:Vincristine; C025430:LY 117018; D003907:Dexamethasone; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone; D008727:Methotrexate