Oestrogenic activity of tamoxifen and its metabolites on gene regulation and cell proliferation in MCF-7 breast cancer cells

Br J Cancer. 1989 May;59(5):727-38. doi: 10.1038/bjc.1989.153.


The effects of tamoxifen, three of its in vivo metabolites and 3-hydroxytamoxifen on cellular proliferation and the induction of four oestrogen-regulated RNAs (pNR-1, pNR-2, pNR-25 and cathepsin D) have been measured in MCF-7 breast cancer cells in phenol red-free culture medium. Tamoxifen and 3-hydroxytamoxifen acted as partial oestrogens to stimulate cell growth and the levels of the pNR-2 and pNR-25 RNAs. They were full oestrogens for the induction of cathepsin D RNA and induced the pNR-1 RNA above the level found in oestrogen-treated cells. N-Desmethyltamoxifen and 4-hydroxytamoxifen behaved like tamoxifen except that N-desmethyltamoxifen did not induce the pNR-2 RNA and was only a partial oestrogen for the induction of cathepsin D RNA, and 4-hydroxytamoxifen did not induce the pNR-2 or pNR-25 RNAs. In the presence of oestradiol, the four anti-oestrogens prevented the stimulation of growth and reduced (pNR-2 and pNR-25) or increased (pNR-1) the RNA levels to those present in MCF-7 cells treated with the anti-oestrogen alone. In contrast, for cathepsin D RNA levels there was a synergistic effect of the anti-oestrogens and oestradiol. The concentration at which each anti-oestrogen was effective was related to its affinity for the oestrogen receptor. Metabolite E was a full oestrogen for the induction of cell proliferation and the oestrogen-regulated RNAs. pNR-25 and pNR-2 RNA levels correlated most closely with effects on cell proliferation. These RNAs are therefore potentially the most useful for predicting the response of breast cancer patients to tamoxifen therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Division / drug effects
  • Estradiol / pharmacology
  • Estrogen Antagonists / therapeutic use*
  • Gene Expression Regulation / drug effects*
  • Humans
  • RNA, Neoplasm / drug effects
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / therapeutic use*
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / pathology


  • Estrogen Antagonists
  • RNA, Neoplasm
  • Tamoxifen
  • droloxifene
  • afimoxifene
  • Estradiol
  • N-desmethyltamoxifen