Insulin-like growth factor binding protein 3 (IGF-BP3) inhibits estrogen-stimulated breast cancer cell proliferation

Biochem Biophys Res Commun. 1994 Jan 14;198(1):292-7. doi: 10.1006/bbrc.1994.1041.

Abstract

We have recently demonstrated that exposure of MCF7 cells to antiestrogens in vitro results in both accumulation of IGF-BP3 in media and reduced mitogenic responsivity to IGFs (Cancer Res. 53:5193-5198). We show here that MCF7 cell proliferation in steroid-stripped, serum containing media is significantly attenuated by rhIGF-BP3 (p < 0.05), with a maximal 40% inhibition of serum stimulated growth achieved by 6.25nM IGF-BP3. 10(-10) M estradiol (E2) significantly stimulated MCF7 proliferation, and co-incubation of estrogen containing cultures with 50nM IGF-BP3 resulted in significant attenuation of the estrogen-stimulated proliferation ([3H]thymidine incorporation: E2, 147 +/- 18% of control; E2 +/- IGF-BP3, 111 +/- 18% of control, p < 0.05). These results demonstrate antagonism of steroid stimulated proliferation by an IGF binding protein and are compatible with the hypothesis that antiestrogen-induced accumulation of IGF-BP3 in the conditioned media of MCF7 cells contributes to the cytostatic action of these drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms
  • Carrier Proteins / pharmacology*
  • Cell Division / drug effects*
  • Cell Line
  • DNA, Neoplasm / biosynthesis
  • DNA, Neoplasm / drug effects
  • Estradiol / pharmacology*
  • Humans
  • Insulin-Like Growth Factor Binding Proteins
  • Kinetics
  • Recombinant Proteins
  • Somatomedins / metabolism
  • Thymidine / metabolism
  • Tumor Cells, Cultured

Substances

  • Carrier Proteins
  • DNA, Neoplasm
  • Insulin-Like Growth Factor Binding Proteins
  • Recombinant Proteins
  • Somatomedins
  • Estradiol
  • Thymidine