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The estrogenic and antiestrogenic activities of tamoxifen and 4-hydroxytamoxifen have been measured on the expression of two estrogen-regulated RNAs (pNR-1 and pNR-2) in the MCF7 human breast cancer cell line cultured in phenol red-free medium. The two antiestrogens increased the level of the pNR-1 RNA to about 80% of the estradiol-induced level, and the induction by estradiol was not significantly antagonized by either antiestrogen. In contrast, the pNR-2 mRNA was only increased to about 10% of the estradiol-induced level, and its induction by estradiol was antagonized by both tamoxifen and 4-hydroxytamoxifen. Thus, the two RNAs respond in dramatically different ways to these antiestrogens. 4-Hydroxytamoxifen and estradiol have similar affinities for the estrogen receptor; however, the induction of both RNAs by 4-hydroxytamoxifen required a 10-fold higher concentration than estradiol for maximum agonist activity, and a 500-fold molar excess was required to antagonize the induction by estradiol. Tamoxifen has a 20-100-fold lower affinity than estradiol for the estrogen receptor. A 200-fold higher concentration was required for maximum agonist activity and a 10,000-fold molar excess to antagonize the induction by estradiol. These results emphasize the complexity of antiestrogen action in human breast cancer cells.
REFERENCES
- Eur. J. Biochem. 1980; 107: 303-314
- Proc. Natl. Acad. Sci. U. S. A. 1986; 83: 2496-2500
- Proc. Natl. Acad. Sci. U. S. A. 1984; 81: 6344-6348
- Lancet. 1986; i: 83-86
- Cancer Res. 1984; 44: 2790-2793
- Cancer Res. 1978; 38: 3352-3364
- Pharmacol. Ther. 1984; 25: 127-205
- Proc. Natl. Acad. Sci. U. S. A. 1980; 77: 5794-5797
- Endocrinology. 1978; 103: 1742-1751
- Nucleic Acids Res. 1984; 12: 2861-2878
- Mol. Pharmacol. 1984; 26: 279-285
- Eur. J. Cancer. 1979; 15: 659-670
- Cell. 1986; 46: 1053-1061
- J. Biol. Chem. 1983; 258: 4741-4745
- Nature. 1975; 256: 592-595
- Nucleic Acids Res. 1982; 10: 7895-7903
- Cancer Res. 1986; 46: 6034-6040
- Nucleic Acids Res. 1984; 12: 7035-7056
- Cancer Res. 1983; 43: 3094-3105
- Breast Cancer Res. Treat. 1982; 2: 363-374
- Eur. J. Cancer Clin. Oncol. 1984; 20: 1419-1424
- Cancer Res. 1985; 45: 1525-1531
- Nature. 1981; 292: 257-259
- Endocrinology. 1985; 117: 561-564
- J. Natl. Cancer Inst. 1973; 51: 1409-1413
- J. Mol. Biol. 1975; 98: 503-517
- Nature. 1980; 288: 273-275
- Revs. Endocrine-related Cancer. 1981; : 134-154
- Nucleic Acids Res. 1987; 15: 3773-3786
- Cell. 1980; 20: 353-362
- J. Biol. Chem. 1984; 259: 10030-10035
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Published online: November 25, 1987
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© 1987 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.
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