Advertisement

Effects of tamoxifen and 4-hydroxytamoxifen on the pNR-1 and pNR-2 estrogen-regulated RNAs in human breast cancer cells.

Open AccessPublished:November 25, 1987DOI:https://doi.org/10.1016/S0021-9258(18)47673-9
      This paper is only available as a PDF. To read, Please Download here.
      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

        • Auffray C.
        • Rougeon F.
        Eur. J. Biochem. 1980; 107: 303-314
        • Berthois Y.
        • Katzenellenbogen J.A.
        • Katzenellenbogen B.S.
        Proc. Natl. Acad. Sci. U. S. A. 1986; 83: 2496-2500
        • Brown A.M.C.
        • Jeltsch J.M.
        • Roberts M.
        • Chambon P.
        Proc. Natl. Acad. Sci. U. S. A. 1984; 81: 6344-6348
        • Cuzick J.
        • Wang D.Y.
        • Bulbrook R.D.
        Lancet. 1986; i: 83-86
        • Darbre P.D.
        • Curtis S.
        • King R.J.B.
        Cancer Res. 1984; 44: 2790-2793
        • Engel L.W.
        • Young N.A.
        • Tralka T.S.
        • Lippman M.E.
        • O'Brien S.J.
        • Joyce M.J.
        Cancer Res. 1978; 38: 3352-3364
        • Furr B.J.A.
        • Jordan V.C.
        Pharmacol. Ther. 1984; 25: 127-205
        • Goldberg D.A.
        Proc. Natl. Acad. Sci. U. S. A. 1980; 77: 5794-5797
        • Horwitz K.B.
        • Koseki Y.
        • McGuire W.L.
        Endocrinology. 1978; 103: 1742-1751
        • Jakowlew S.B.
        • Breatnach R.
        • Jeltsch J-M.
        • Masiakowski P.
        • Chambon P.
        Nucleic Acids Res. 1984; 12: 2861-2878
        • Jordan V.C.
        • Lieberman M.E.
        Mol. Pharmacol. 1984; 26: 279-285
        • Keydar I.
        • Chen L.
        • Karby S.
        • Weiss F.R.
        • Delarea J.
        • Radu M.
        • Chaitcik S.
        • Brenner H.J.
        Eur. J. Cancer. 1979; 15: 659-670
        • Klein-Hitpass L.
        • Schorpp M.
        • Wagner U.
        • Ryffel G.U.
        Cell. 1986; 46: 1053-1061
        • Lieberman M.E.
        • Gorski J.
        • Jordan V.C.
        J. Biol. Chem. 1983; 258: 4741-4745
        • Lippman M.E.
        • Bolan G.
        Nature. 1975; 256: 592-595
        • Masiakowski P.
        • Breathnach R.
        • Bloch J.
        • Gannon F.
        • Krust A.
        • Chambon P.
        Nucleic Acids Res. 1982; 10: 7895-7903
        • May F.E.B.
        • Westley B.R.
        Cancer Res. 1986; 46: 6034-6040
        • Melton D.A.
        • Krieg P.A.
        • Rebagliati M.R.
        • Maniatis T.
        • Zinn K.
        • Green G.R.
        Nucleic Acids Res. 1984; 12: 7035-7056
        • Millar M.A.
        • Katzenellenbogen B.S.
        Cancer Res. 1983; 43: 3094-3105
        • Patterson J.S.
        • Furr B.
        • Wakeling A.
        • Battersby L.
        Breast Cancer Res. Treat. 1982; 2: 363-374
        • Reddell R.R.
        • Sutherland R.L.
        Eur. J. Cancer Clin. Oncol. 1984; 20: 1419-1424
        • Reddell R.R.
        • Murphy L.C.
        • Hall R.E.
        • Sutherland R.L.
        Cancer Res. 1985; 45: 1525-1531
        • Rochefort H.
        • Borgna J-L.
        Nature. 1981; 292: 257-259
        • Sheen Y.Y.
        • Simpson D.M.
        • Katzenellenbogen B.S.
        Endocrinology. 1985; 117: 561-564
        • Soule H.D.
        • Vasquez J.
        • Lang A.
        • Albert S.
        • Brennan M.A.
        J. Natl. Cancer Inst. 1973; 51: 1409-1413
        • Southern E.M.
        J. Mol. Biol. 1975; 98: 503-517
        • Sutherland R.L.
        • Murphy L.C.
        • Foo M.S.
        • Green M.D.
        • Whybourne A.M.
        Nature. 1980; 288: 273-275
        • Wakeling A.
        • Slater S.R.
        Revs. Endocrine-related Cancer. 1981; : 134-154
        • Westley B.R.
        • May F.E.B.
        Nucleic Acids Res. 1987; 15: 3773-3786
        • Westley B.
        • Rochefort H.
        Cell. 1980; 20: 353-362
        • Westley B.
        • May F.E.B.
        • Brown A.M.C.
        • Krust A.
        • Chambon P.
        • Lippman M.E.
        • Rochefort H.
        J. Biol. Chem. 1984; 259: 10030-10035