Biology of insulin-like growth factor binding protein-4 and its role in cancer (review).

Insulin-like growth factor binding protein-4 (IGFBP-4) is an important member of the insulin-like growth factor (IGF) system. The IGFBP-4 has three domains of which the N-terminal sequence is important for the binding of IGF. It acts as a transport protein for IGF-I and IGF-II and modulates their biological effects. There is increasing evidence that IGFBP-4 inhibits IGF-induced cellular growth both in vitro and in vivo. IGFBP-4 can also mediate its actions through a mechanism independent of IGFs. IGFBP-4 level and expression in various tissues are influenced by IGFBP protease, nutrition, several growth factors and hormones. Overexpression of IGFBP-4 in transgenic animal models causes reduced growth of organs containing smooth muscle. Most cancers express IGFBP-4 at levels which correlate with their state of differentiation. However, the effects of IGFBP-4 on tumor growth are uncertain. In vitro studies have shown that overexpression of IGFBP-4 inhibit the growth of some colon cancer cells. Overexpression of IGFBP-4 in vivo has been reported to decrease the growth of prostate cancer. The effect of altered expression of IGFBP-4 in vivo in colon and other cancers needs to be explored as locally available IGFs appear to stimulate mitogenesis.
AuthorsRajaraman Durai, Mark Davies, Wenxuan Yang, Shi Yu Yang, Alexander Seifalian, Geoffrey Goldspink, Marc Winslet
JournalInternational journal of oncology (Int J Oncol) Vol. 28 Issue 6 Pg. 1317-25 (Jun 2006) ISSN: 1019-6439 [Print] Greece
PMID16685432 (Publication Type: Journal Article, Review)
Chemical References
  • Insulin-Like Growth Factor Binding Protein 4
  • Animals
  • Cell Division (drug effects, physiology)
  • Cell Line, Tumor
  • Disease Models, Animal
  • Humans
  • Insulin-Like Growth Factor Binding Protein 4 (genetics, pharmacology, physiology)
  • Male
  • Neoplasms (pathology)
  • Prostatic Neoplasms (pathology)

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