High progesterone receptor concentration in a variant of the ZR-75-1 human breast cancer cell line adapted to growth in oestrogen free conditions.
Culture of ZR-75-1 human breast cancer cells for 5 days in the absence of oestrogens (phenol red-free medium supplemented with dextran coated charcoal stripped 5% fetal calf serum) resulted in a slowing of growth rate and loss of progesterone receptors. Oestradiol at 10(-9) M markedly stimulated growth and progesterone receptor synthesis over a 5-day period. While medroxyprogesterone acetate (10(-10) to 10(-6) M) inhibited growth of ZR-75-1 cells growing in complete medium, in the short-term absence of oestrogens low concentrations were growth stimulatory. Cells deprived of oestrogens for 5 days retained sensitivity to growth inhibition by 4-hydroxy tamoxifen. ZR-75-1 cells were also adapted to growth in the absence of oestrogens over a 5-month period. These cells (ZR-PR-LT) failed to express binding sites characteristic of the type 1 oestrogen receptor but progesterone receptor expression was at a level normally associated with oestrogen induction. Adapted cells were growth inhibited by oestradiol, 4-hydroxy tamoxifen and medroxyprogesterone acetate, but despite elevated progesterone receptor expression the progestin was only marginally more inhibitory than in the parent line. Our data indicate a poor quantitative relationship between response to progestins in vitro and progesterone receptor concentration and support previous findings that acquisition of an oestrogen independent phenotype does not necessarily result in resistance to anti-oestrogens.
van den Berg
H W
HW
Department of Therapeutics and Pharmacology, Queen's University of Belfast, Northern Ireland.
Martin
J
J
Lynch
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000032:analysis* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003271:Contraceptive Agents, Female / Q000494:pharmacology; D003470:Culture Media; D004958:Estradiol / Q000502:physiology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D006801:Humans; D008525:Medroxyprogesterone / Q000031:analogs & derivatives / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D011980:Receptors, Progesterone / Q000032:analysis*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D003271:Contraceptive Agents, Female; D003470:Culture Media; D004965:Estrogen Antagonists; D011980:Receptors, Progesterone; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone