Counteraction of estradiol‐induced activation of tissue‐type plasminogen activator in a human breast cancer cell line by an anti‐estrogen, LY117018

LY117018 is a non‐steroid anti‐estrogen which exhibits about 100 times higher affinity for estrogen receptor than tamoxifen, another anti‐estrogen. The cell line ES‐1, which was isolated from human breast cancer MCF‐7 cells, was highly sensitive to the cytocidal action of estradiol. Growth of ES‐I cells was inhibited by 10⁻⁸M 17 β‐estradiol, a concentration that stimulated the growth of parental MCF‐7 cells. The estradiol‐induced growth inhibition of ES‐1 cells was almost completely reversed by treatment with LY 117018, but not by treatment with tamoxifen. The relative binding affinity of LYI17018 for estradiol receptor was equal to that of estradiol in both MCF‐7 and ES‐1 cells. Treatment of ES‐1 cells with estradiol specifically induced tissue‐type plasminogen activator (t‐PA), whereas such estradiol‐induced activation was not observed in parental MCF‐7 cells. Quantitative immunoreac‐tive assays and Northern blot analysis showed that estradiol‐induced expression of t‐PA was blocked by LYI 17018 in ES‐1 cells. The inhibitory effect of tamoxifen was about 100 times lower than that of LYI 17018. The inhibition of t‐PA gene expression by LYI 17018 might be due to competitive inhibition with estradiol in estradiol receptor binding.