IGFBP-6 five years on; not so 'forgotten'?

Abstract

Insulin-like growth factor binding protein (IGFBP)-6 is unique among IGFBPs for its IGF-II binding specificity. IGFBP-6 inhibits growth of a number of IGF-II-dependent cancers, including rhabdomyosarcoma, neuroblastoma and colon cancer. Although the major action of IGFBP-6 appears to be inhibition of IGF-II actions, a number of studies suggest that it may also have IGF-independent actions. Gene array studies show regulation of IGFBP-6 in many circumstances that are consistent with antiproliferative actions. However, other studies show the opposite, so that IGFBP-6 may be acting as a counter-regulator in these situations or it may have other as yet undetermined actions. Both the N-terminal and C-terminal domains of IGFBP-6 contribute to high affinity IGF binding, and the C-terminal domain appears to confer its IGF-II specificity. The three-dimensional structure of the C-domain of IGFBP-6 contains a thyroglobulin type 1 fold, and the IGF-II binding site is located in the proximal half of this domain adjacent to the glycosaminoglycan binding site. Future studies are needed to further delineate the putative IGF-independent actions of IGFBP-6 and to build on the structural information to enhance our understanding of this IGFBP. This is particularly significant since IGFBP-6 provides an attractive basis for therapy of IGF-II-dependent tumors.

• Authors: Leon A Bach
• Journal: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society (Growth Horm IGF Res) Vol. 15 Issue 3 Pg. 185-92 (Jun 2005) ISSN: 1096-6374 [Print] Scotland
• PMID: 15914054 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Insulin-Like Growth Factor Binding Protein 6
• Insulin-Like Growth Factor II

Topics

• Animals
• Central Nervous System (metabolism)
• Gene Expression Profiling
• Gene Expression Regulation
• Humans
• Insulin-Like Growth Factor Binding Protein 6 (chemistry, genetics, physiology)
• Insulin-Like Growth Factor II (metabolism)
• Mice
• Mice, Transgenic
• Neoplasms (metabolism)
• Oligonucleotide Array Sequence Analysis
• Protein Conformation