Type I IGF receptor and acquired tamoxifen resistance in oestrogen-responsive human breast cancer cells

Eur J Cancer. 1993;29A(16):2256-64. doi: 10.1016/0959-8049(93)90218-5.


Tamoxifen inhibited the oestrogen-stimulated proliferation of MCF-7 cells but had little effect on the oestrogen-stimulated proliferation of two tamoxifen-resistant variants (RL-3 and AL-1). The lack of oestrogen antagonist activity in the resistant cells was largely a result of an increased oestrogen agonist activity of tamoxifen on cell proliferation. Proliferation of the tamoxifen-resistant cells was also stimulated by 4-hydroxytamoxifen but not by ICI 164,384, a structurally distinct pure anti-oestrogen. Tamoxifen does not have increased oestrogen agonist activity for the induction of a series of oestrogen-regulated RNAs, and this suggests that the increased agonist activity may be restricted to key components involved in the proliferative response. Tamoxifen-stimulated cell proliferation was dependent on insulin-like growth factor I (IGF-1) in the resistant cells, suggesting that tamoxifen stimulates cell proliferation by sensitising cells to the proliferative effects of IGF-1. This may involve induction of the type-I IGF receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Cell Adhesion
  • Cell Division / drug effects
  • Dose-Response Relationship, Drug
  • Drug Resistance
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Estrogen Antagonists / pharmacology
  • Estrogens / pharmacology
  • Female
  • Humans
  • Insulin-Like Growth Factor I / pharmacology
  • Polyunsaturated Alkamides
  • Receptor, IGF Type 1 / physiology*
  • Tamoxifen / pharmacology*
  • Tumor Cells, Cultured


  • Estrogen Antagonists
  • Estrogens
  • Polyunsaturated Alkamides
  • Tamoxifen
  • Estradiol
  • Insulin-Like Growth Factor I
  • ICI 164384
  • Receptor, IGF Type 1