Counteraction of estradiol-induced activation of tissue-type plasminogen activator in a human breast cancer cell line by an anti-estrogen, LY117018
✍ Scribed by T. Uchiumi; H. Mizoguchi; Y. Hagino; K. Kohno; M. Kuwano
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- French
- Weight
- 718 KB
- Volume
- 47
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
L Y I 17018 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-I , 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%1 17 P-estradiol, a concentration that stimulated the growth of parental MCF-7 cells. The estradiol-induced growth inhibition of ES-I cells was almost completely reversed by treatment with LY I 17018, but not by treatment with tamoxifen. The relative binding affinity of LY I 17018 for estradiol receptor was equal to that of estradiol in both MCF-7 and ES-I cells. Treatment of ES-I 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 immunoreactive assays and Northern blot analysis showed that estradiolinduced expression of t-PA was blocked by LY I I701 8 in ES-I cells. The inhibitory effect of tamoxifen was about 100 times lower than that of LY117018. The inhibition of t-PA gene expression by LY I17018 might be due to competitive inhibition with estradiol in estradiol receptor binding.