title: Physiology and pathophysiology of IGFBP-1 and IGFBP-2 - consensus and dissent on metabolic control and malignant potential.
abstract: IGFBP-1 and IGFBP-2 are suppressed by growth hormone and therefore represent less prominent members of the IGFBP family when compared to IGFBP-3 that carries most of the IGFs during circulation under normal conditions in humans in vivo. As soon as the GH signal is decreased expression of IGF-I and IGFBP-3 is reduced. Under conditions of lowered suppression by GH the time seems come for IGFBP-1 and IGFBP-2. Both IGFBPs are potent effectors of growth and metabolism. Secretion of IGFBP-1 and IGFBP-2 is further suppressed by insulin and diminished with increasing obesity. Both IGFBP family members share the RGD sequence motif that mediates binding to integrins and is linked to PTEN/PI3K signalling. In mice, IGFBP-2 prevents age- and diet-dependent glucose insensitivity and blocks differentiation of preadipocytes. The latter function is modulated by two distinct heparin-binding domains of IGFBP-2 which are lacking in IGFBP-1. IGFBP-2 is further regulated by leptin and has been demonstrated to affect insulin sensitivity and glucose tolerance, further supporting a particular role of IGFBP-2 in glucose and fat metabolism. Since IGFBP-2 is controlled by sex steroids as well, we devised a scheme to compare IGFBP effects in breast, ovarian and prostate cancer. While a positive association does not seem to exist with IGFBP-1 and risk of cancers within these reproductive tissues, a relationship between IGFBP-2 and breast cancer, ovarian cancer and prostate cancer does indeed appear to be present. To date, the specific roles of IGFBP-2 in estrogen signalling are unclear, though there is accumulating evidence for an effect of IGFBP-2 on PI3K signalling via PTEN, particularly in breast cancer.
authors.affiliation: Institute for Genome Biology, Leibniz-Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany. Electronic address: hoeflich@fbn-dummerstorf.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoeflich
authors.affiliation: Hormone Research, Murdoch Childrens Research Institute, Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia. Electronic address: vince.russo@mcri.edu.au.
authors.forename: Vincenzo C
authors.initials: VC
authors.lastname: Russo
mesh_terms: D000818:Animals; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008659:Metabolic Diseases / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D013002:Somatomedins
keywords: AKT; IGFBP-1; IGFBP-2; PTEN; cancer; diabetes; metabolism; obesity; steroids