Insulin-like growth factor-I and its autocrine role in growth of MCF-7 human breast cancer cells in culture

J Mol Endocrinol. 1989 Nov;3(3):183-90. doi: 10.1677/jme.0.0030183.

Abstract

Human MCF-7 breast cancer cells have been studied to determine their suitability as an autocrine model for the synthesis, secretion and action of insulin-like growth factor-I (IGF-I). Secretion of immunoreactive (ir-) IGF-I into serum-free medium was very low (less than 500 pg/10(6) cells per day). Northern blot hybridization detected at least two IGF-I messenger RNA transcripts (approximately 4.6 and approximately 1.8 kb) which were similar in size to those reported in other human and rat tissues. IGF-II mRNA was also detected but at low abundance. Cell proliferation was stimulated in a dose-responsive manner by exogenous IGF-I (10-30 ng/ml). Addition of a monoclonal antibody against IGF-I to MCF-7 cells in serum-free medium caused an inhibition of cell proliferation, suggesting that endogenous locally produced IGF-I does play an autocrine/paracrine role in MCF-7 cell growth. Proliferation of MCF-7 cells was sensitive to oestradiol (10 nM) in the absence but not in the presence of the weakly oestrogenic pH indicator phenol red. Neither IGF-I secretion nor IGF-I mRNA synthesis, however, was affected by addition of oestradiol. Similarly, GH, dexamethasone or dexamethasone plus oestradiol had no effect on either parameter. These data indicate that MCF-7 cells synthesize, secrete and respond to IGF-I. The very low levels of ir-IGF-I produced and their apparent lack of hormonal modulation suggest, however, that further studies are required to establish whether IGF-I plays a major physiological role in growth and development of MCF-7 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Blotting, Northern
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Division
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Drug
  • Estradiol / pharmacology
  • Female
  • Growth Hormone / pharmacology
  • Humans
  • Insulin-Like Growth Factor I / biosynthesis
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology
  • Insulin-Like Growth Factor I / physiology*
  • Insulin-Like Growth Factor II / genetics
  • Models, Biological
  • Phenolsulfonphthalein / pharmacology
  • RNA, Messenger / analysis
  • Rats
  • Somatomedins / physiology*
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • RNA, Messenger
  • Somatomedins
  • Estradiol
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Dexamethasone
  • Growth Hormone
  • Phenolsulfonphthalein