scholarly journals Insulin-Like Growth Factor (IGF)-Binding Protein-3 (IGFBP-3) Binds to Fibronectin (FN): Demonstration of IGF-I/IGFBP-3/FN Ternary Complexes in Human Plasma1

2001 ◽  
Vol 86 (5) ◽  
pp. 2104-2110 ◽  
Author(s):  
Yaoting Gui ◽  
Liam J. Murphy
Keyword(s):  
Growth Factor ◽  
Ternary Complexes ◽  
Insulin Like Growth Factor ◽  
Heparin Binding ◽  
Complementary Dna ◽  
Igf I ◽  
Igf Binding ◽  
Carboxyl Terminal ◽  
Igf Binding Protein ◽  
Igfbp 3

We used a yeast two-hybrid system to identify binding partners for insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3). A partial complementary DNA encoding the carboxyl-terminal of fibronectin (FN), including the cell binding site, the heparin-binding domain, and the fibrin-binding domain, was identified in a screen of a human placental complementary DNA library. The interaction of IGFBP-3 with FN and the 40-kDa heparin-binding carboxyl-terminal fragment of FN was confirmed using Western ligand blotting. Both glycosylated and nonglycosylated IGFBP-3 bound to FN with a Kd of approximately 0.3 nmol/L. IGF-I and IGFBP-1 had no effect on IGFBP-3 binding to FN. Competitive inhibition of IGFBP-3 binding to FN was observed in the presence of IGFBP-5 and heparin. The binding affinity of the immobilized IGFBP-3/FN complex for [125I]IGF-I (Kd = 0.8 nmol/L) was similar to that of IGFBP-3 alone. The presence of IGF-I/IGFBP-3/FN ternary complexes in human plasma was demonstrated by coimmunoprecipitation of IGFBP-3 and [125I]IGF-I with anti-FN monoclonal antibody. These data indicate that FN may have a role in the transportation of IGFBP-3 and IGF-I in the circulation and the sequestration of these proteins in tissues.

Specimen processing time and measurement of total insulin-like growth factor-I (IGF-I), free IGF-I, and IGF binding protein-3 (IGFBP-3)

2006 ◽  
Vol 16 (2) ◽  
pp. 86-92 ◽  
Author(s):  
Tiffany G. Harris ◽  
Howard D. Strickler ◽  
Herbert Yu ◽  
Michael N. Pollak ◽  
E. Scott Monrad ◽  
...  
Keyword(s):  
Growth Factor ◽  
Processing Time ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Specimen Processing ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

scholarly journals Genetic Determinants of Circulating Insulin-Like Growth Factor (IGF)-I, IGF Binding Protein (BP)-1, and IGFBP-3 Levels in a Multiethnic Population

2007 ◽  
Vol 92 (9) ◽  
pp. 3660-3666 ◽  
Author(s):  
Iona Cheng ◽  
Katherine DeLellis Henderson ◽  
Christopher A. Haiman ◽  
Laurence N. Kolonel ◽  
Brian E. Henderson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Genetic Determinants ◽  
Igf I ◽  
Igf Binding ◽  
Multiethnic Population ◽  
Igf Binding Protein ◽  
Igfbp 3

scholarly journals Steroid Receptor Coactivator 3 Maintains Circulating Insulin-Like Growth Factor I (IGF-I) by Controlling IGF-Binding Protein 3 Expression

2008 ◽  
Vol 28 (7) ◽  
pp. 2460-2469 ◽  
Author(s):  
Lan Liao ◽  
Xian Chen ◽  
Shu Wang ◽  
Albert F. Parlow ◽  
Jianming Xu
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Steroid Receptor Coactivator ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

ABSTRACT Steroid receptor coactivator 3 (SRC-3/AIB1/ACTR/NCoA-3) is a transcriptional coactivator for nuclear receptors including vitamin D receptor (VDR). Growth hormone (GH) regulates insulin-like growth factor I (IGF-I) expression, and IGF-I forms complexes with acid-labile subunit (ALS) and IGF-binding protein 3 (IGFBP-3) to maintain its circulating concentration and endocrine function. This study demonstrated that the circulating IGF-I was significantly reduced in SRC-3−/− mice with the C57BL/6J background. However, SRC-3 deficiency affected neither GH nor ALS expression. The low IGF-I level in SRC-3−/− mice was not due to the failure of IGF-I mRNA and protein synthesis but was a consequence of rapid degradation. The rapid IGF-I degradation was associated with drastically reduced IGFBP-3 levels. Because IGF-I and IGFBP-3 stabilize each other, SRC-3−/− mice were crossbred with the liver-specific transthyretin (TTR)-IGF-I transgenic mice to assess the relationship between reduced IGF-I and IGFBP-3. In SRC-3−/−/TTR-IGF-I mice, the IGF-I level was significantly increased over that in SRC-3−/− mice, but the IGFBP-3 level failed to increase proportionally, indicating that the low IGFBP-3 level is a responsible factor that limits the IGF-I level in SRC-3−/− mice. Furthermore, IGFBP-3 mRNA was reduced in SRC-3−/− mice. The IGFBP-3 promoter activity induced by vitamin D, through VDR, was diminished in SRC-3−/− cells, suggesting an important role of SRC-3 in VDR-mediated transactivation of the IGFBP-3 gene. In agreement with the role of SRC-3 in VDR function, the expression of several VDR target genes was also reduced in SRC-3−/− mice. Therefore, SRC-3 maintains IGF-I in the circulation through enhancing VDR-regulated IGFBP-3 expression.

scholarly journals Circulating Insulin-Like Growth Factor II and Colorectal Adenomas*

2000 ◽  
Vol 85 (9) ◽  
pp. 3402-3408 ◽  
Author(s):  
Andrew G. Renehan ◽  
John E. Painter ◽  
Domhnall O’Halloran ◽  
Wendy S. Atkin ◽  
Christopher S. Potten ◽  
...  
Keyword(s):  
Growth Factor ◽  
Positive Association ◽  
Colorectal Adenomas ◽  
Insulin Like Growth Factor ◽  
Trial Entry ◽  
Igf I ◽  
Igf Binding ◽  
Immunohistochemical Studies ◽  
Igf Binding Protein ◽  
Igfbp 3

Abstract Circulating insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) may be risk factors for the development of colorectal cancer. On the other hand, IGF-II and IGFBP-2 are overexpressed in colorectal carcinomas. These contrasting backgrounds led us to investigate the relationship between serum IGF-I, IGF-II, IGFBP-2, and IGFBP-3 and the presence of colorectal adenomas, known precursors of colorectal carcinoma, in 345 volunteers attending a screening flexible sigmoidoscopy trial (entry criteria: healthy, aged 55–64 yr). The most striking finding was an elevated mean serum IGF-II in individuals with adenomas (n = 52) compared with controls (mean difference, 139 ng/mL; 95% confidence intervals, 82, 196; P < 0.0001). Logistic regression adjusting for confounding factors confirmed the significant association between IGF-II and adenoma occurrence (P < 0.0001) and revealed an additional positive association with serum IGFBP-2 (P < 0.0001). However, there was no association found between either serum IGF-I and/or IGFBP-3 and the presence of adenomas. Additionally, in 31 individuals with adenomas in whom levels were determined pre- and postpolypectomy, there was a significant fall in mean IGF-II (P < 0.001) and IGFBP-2 (P < 0.001) after adenoma removal, but no difference in IGF-II and IGFBP-2 concentrations between repeated samples in 20 individuals without adenomas. Immunohistochemical studies demonstrated IGF-II expression in 83% of all adenomas, which contrasted with absent expression in normal colonic expression and hyperplastic polyps. This study has shown for the first time that serum IGF-II may be a tumor marker in individuals with colorectal adenomas. Further studies are needed to validate these relationships in larger populations, including individuals undergoing colonoscopy.

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