RECEPTOR STATUS AND SUBSEQUENT SENSITIVITY OF SUBCLONES OF MCF-7 HUMAN-BREAST CANCER-CELLS SURVIVING EXPOSURE TO DIETHYLSTILBESTROL

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (6) , 2831-2835
Abstract
The estrogen receptor (ER)-positive human breast cancer cell line MCF-7 was incubated continuously in the presence of pharmacological concentrations of diethylstilbestrol (DES) to correlate receptor status with DES sensitivity. Cytotoxicity occurred at DES concentrations > 5 .times. 10-6 M; however, a small percentage of cells, both from the wild-type MCF-7 line and from subclones derived in soft agar from single MCF-7 cells, survived, with altered morphology, up to 4 mo. of continuous exposure to DES concentrations ranging from 5 .times. 10-6-1 .times. 10-4 M. Characterization of 7 regenerated surviving cell populations suggested that they remained ER positive; no evidence could be found for a block in the pathway of hormonal activation, as determined by progesterone receptor induction, to explain the ability of these cells to survive DES. Three regenerated cell populations were reexposed to DES. Two remained as sensitive to growth inhibition as untreated parent cells from which they were derived; however, one of these, designated MCF-7(35-1), had autonomously high progesterone receptor (463 .+-. 94 fmol/mg of cytosol; Kd = 1.8 .+-. 0.2 .times. 10-9 M) which was not significantly stimulated by the addition of 1 .times. 10-8 M 17.beta.-estradiol for 72 h. The 3rd population, designated MCF-7(35-3), which survived initial exposure to 5 .times. 10-5 M DES for 109 days and which remained ER positive (27 .+-. 3 fmol/mg of cytosol; Kd = 0.8 .+-. 0.2 .times. 10-10 M) and progesterone receptor inducible, demonstrated significantly decreased sensitivity (P = 0.025) on reexposure to DES; conversely, significantly increased sensitivity (P < 0.03) to the antiestrogen tamoxifen was observed. The mechanisms by which some MCF-7 cells survive prolonged exposure to DES are not certain; there is no clear relationship between ER status and sensitivity to DES and there apparently is no way of predicting the ultimate status of cells surviving DES treatment.