Altered expression of the IGF-1 receptor in a tamoxifen-resistant human breast cancer cell line

Br J Cancer. 1999 Feb;79(5-6):693-700. doi: 10.1038/sj.bjc.6690112.


The relationship between oestrogen (E2) and insulin-like growth factor-one (IGF-1) was examined in both tamoxifen-sensitive (MCF 7/5-21) and tamoxifen-resistant (MCF 7/5-23) subclones of the MCF 7 cell line. Both subclones were grown in defined, serum-free (SF) medium over a period of 7 days with the addition of E2 or IGF-1 or a combination of both agents. Growth of both MCF 7/5-21 and 7/5-23 cells was stimulated (245% and 350%, respectively) by E2. However, only the growth of MCF 7/5-23 cells was stimulated (266%) by IGF-1. A combination of E2 and IGF-1 significantly enhanced MCF 7/5-21 and 7/5-23 cell growth (581% and 695%, respectively). E2-induced IGF-1 receptor (IGF-1R) levels (as measured by 125I-IGF-1 binding and Northern analyses) in only MCF 7/5-23 cells. This effect was partially inhibited by tamoxifen. In medium containing serum, the growth of only the MCF 7/5-23 cells was significantly inhibited by the IGF-1R monoclonal antibody, alphaIR-3. The detection of E2-induced expression of IGF-2 using RT-PCR was demonstrated in the MCF 7/5-23 cells. These experiments indicate that E2 may sensitize tamoxifen-resistant MCF 7/5-23 cells to the growth stimulatory actions of IGF-2 via up-regulation of the IGF-1R and describes a cell-survival mechanism that may manifest itself as tamoxifen resistance.

MeSH terms

  • Breast Neoplasms / metabolism*
  • Cell Division / drug effects
  • Clone Cells
  • Culture Media, Serum-Free
  • Drug Resistance, Neoplasm*
  • Estradiol / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Histones / genetics
  • Humans
  • Insulin-Like Growth Factor I / pharmacology
  • Insulin-Like Growth Factor II / genetics
  • Kinetics
  • Receptor, IGF Type 1 / genetics*
  • Receptor, IGF Type 1 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tamoxifen / toxicity*
  • Transcription, Genetic
  • Tumor Cells, Cultured


  • Culture Media, Serum-Free
  • Histones
  • Tamoxifen
  • Estradiol
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Receptor, IGF Type 1