Human mammary cancer cell mutants with altered hormone receptor activity.
We have recently isolated retinoic acid-resistant clones U-2 and U-3 from human breast cancer cell line MCF-7 (Ueda et al. (1985) Cancer Res. 45, 3332-3338). Growth of MCF-7 cells was found to be stimulated by estradiol but that of U-2 or U-3 was not. Cytosol from U-2 or U-3 cells contained no detectable estradiol receptor activity, whereas that from the parental MCF-7 cells showed estradiol receptor activity of 32 fmol/mg cytosol protein with a Kd of 2.6 X 10(-10) M by Scatchard analysis. Sucrose gradient centrifugation analysis of the cytosol fraction confirmed the presence of estradiol receptor activity in MCF-7 but not in U-2. Cytosol from MCF-7 and U-2 cells showed progesterone receptor activities of 106 fmol/mg protein with a Kd of 7.4 X 10(-10) M and 13 fmol/mg protein with a Kd of 9.9 X 10(-10) M, respectively. Addition of estradiol to the culture medium of the cells increased the level of progesterone receptor about 2-fold in MCF-7, but not in U-2. U-2 or U-3 cells showed about 5-fold higher resistance to an antiestrogen, tamoxifen, than MCF-7, and they were also 300- to 1,000-fold more resistant to other antiestrogens, epitiostanol and medroxyprogesterone, than MCF-7. The altered cellular sensitivity of U-2 or U-3 to the hormone antagonists is discussed in relation to the absence or presence of hormone receptors.
D000732:Androstanols / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007700:Kinetics; D009154:Mutation; D011397:Promegestone / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011959:Receptors, Estradiol / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology
D000732:Androstanols; D011956:Receptors, Cell Surface; D011959:Receptors, Estradiol; D011980:Receptors, Progesterone; D013629:Tamoxifen; D004958:Estradiol; D011397:Promegestone; C002976:epitiostanol