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Modulation by retinoic acid of insulin-like growth factor (IGF) and IGF binding protein expression in human SK-N-SH neuroblastoma cells.

Abstract
Growth in neuroblastoma cells is regulated by insulin-like growth factors (IGFs) whose action is modulated by IGF binding proteins (IGFBPs). In this study, SK-N-SH neuroblastoma cells were shown to produce IGF-II, IGFBP-2, IGFBP-4 and small quantities of IGFBP-6. We have studied the effects of a natural morphogen, retinoic acid (RA), on growth and IGFBP expression in these cells. In all experiments, cells were cultured in serum-free medium and treated with 1 mumol/l RA for 12 h. Cell number increased by almost 50% during the first 24 h after the beginning of treatment. This stimulation was inhibited by 80% or more in the presence of the anti-type 1 IGF receptor antibody alpha-IR3 and anti-IGF-II antibody. The IGF-II concentrations in the culture media, measured after acidic gel filtration, increased about 1.5-fold and Northern blotting showed a concomitant increase in IGF-II mRNA levels. The mitogenic effect of RA therefore reflects its stimulation of IGF-II production. The availability of IGF-II to the cells may also be enhanced because of the proteolysis of IGFBP-2 to which it is bound. After this initial phase, proliferation ceased despite continued IGF-II production between 24 and 72 h. Both IGFBP-2 and IGFBP-4 production decreased, whereas that of IGFBP-6 increased. These changes appeared both in the protein quantities and in their mRNAs. Insulin-like growth factor binding protein 6 has a strong affinity for IGF-II, 5-10 times that of IGFBP-2 and at least 10 times that of the type I IGF receptor, and the arrested proliferation may result, at least in part, from sequestration by IGFBP-6 of the IGF-II secreted.
AuthorsS Babajko, M Binoux
JournalEuropean journal of endocrinology / European Federation of Endocrine Societies (Eur J Endocrinol) Vol. 134 Issue 4 Pg. 474-80 (Apr 1996) ISSN: 0804-4643 [Print] NORWAY
PMID8640300 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Insulin-Like Growth Factor Binding Protein 2
  • Insulin-Like Growth Factor Binding Protein 4
  • Insulin-Like Growth Factor Binding Protein 6
  • Insulin-Like Growth Factor Binding Proteins
  • RNA, Messenger
  • Tretinoin
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
Topics
  • Blotting, Western
  • Cell Division
  • Gene Expression (drug effects)
  • Humans
  • Insulin-Like Growth Factor Binding Protein 2 (genetics)
  • Insulin-Like Growth Factor Binding Protein 4 (genetics)
  • Insulin-Like Growth Factor Binding Protein 6 (genetics)
  • Insulin-Like Growth Factor Binding Proteins (genetics)
  • Insulin-Like Growth Factor I (genetics, pharmacology)
  • Insulin-Like Growth Factor II (genetics, pharmacology)
  • Neuroblastoma (metabolism, pathology)
  • RNA, Messenger (metabolism)
  • Tretinoin (pharmacology)
  • Tumor Cells, Cultured

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