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Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia
Correspondence: Address all correspondence and requests for reprints to: Robert C. Baxter, Ph.D., D.Sc., Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia. E-mail: robaxter{at}med.usyd.edu.au
In addition to their roles in IGF transport, the six IGF-binding proteins (IGFBPs) regulate cell activity in various ways. By sequestering IGFs away from the type I IGF receptor, they may inhibit mitogenesis, differentiation, survival, and other IGF-stimulated events. IGFBP proteolysis can reverse this inhibition or generate IGFBP fragments with novel bioactivity. Alternatively, IGFBP interaction with cell or matrix components may concentrate IGFs near their receptor, enhancing IGF activity. IGF receptor-independent IGFBP actions are also increasingly recognized. IGFBP-1 interacts with
5ß1 integrin, influencing cell adhesion and migration. IGFBP-2, -3, -5, and -6 have heparin-binding domains and can bind glycosaminoglycans. IGFBP-3 and -5 have carboxyl-terminal basic motifs incorporating heparin-binding and additional basic residues that interact with the cell surface and matrix, the nuclear transporter importin-ß, and other proteins. Serine/threonine kinase receptors are proposed for IGFBP-3 and -5, but their signaling functions are poorly understood. Other cell surface IGFBP-interacting proteins are uncharacterized as functional receptors. However, IGFBP-3 binds and modulates the retinoid X receptor-
, interacts with TGFß signaling through Smad proteins, and influences other signaling pathways. These interactions can modulate cell cycle and apoptosis. Because IGFBPs regulate cell functions by diverse mechanisms, manipulation of IGFBP-regulated pathways is speculated to offer therapeutic opportunities in cancer and other diseases.
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S. Mukherjee and C. Guidry The Insulin-Like Growth Factor System Modulates Retinal Pigment Epithelial Cell Tractional Force Generation Invest. Ophthalmol. Vis. Sci., April 1, 2007; 48(4): 1892 - 1899. [Abstract] [Full Text] [PDF] |
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J. L. Eiseman, J. Guo, R. K. Ramanathan, C. P. Belani, D. B. Solit, H. I. Scher, S. P. Ivy, E. G. Zuhowski, and M. J. Egorin Evaluation of Plasma Insulin-like Growth Factor Binding Protein 2 and Her-2 Extracellular Domain as Biomarkers for 17-Allylamino-17-Demethoxygeldanamycin Treatment of Adult Patients with Advanced Solid Tumors Clin. Cancer Res., April 1, 2007; 13(7): 2121 - 2127. [Abstract] [Full Text] [PDF] |
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Y. Yin, J. Ni, M. Chen, M. A. DiMaggio, Y. Guo, and S. Yeh The Therapeutic and Preventive Effect of RRR-{alpha}-Vitamin E Succinate on Prostate Cancer via Induction of Insulin-Like Growth Factor Binding Protein-3 Clin. Cancer Res., April 1, 2007; 13(7): 2271 - 2280. [Abstract] [Full Text] [PDF] |
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O. Shynlova, P. Tsui, A. Dorogin, B. L. Langille, and S. J. Lye Insulin-like Growth Factors and Their Binding Proteins Define Specific Phases of Myometrial Differentiation During Pregnancy in the Rat Biol Reprod, April 1, 2007; 76(4): 571 - 578. [Abstract] [Full Text] [PDF] |
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G. Walker, K. MacLeod, A. R.W. Williams, D. A. Cameron, J. F. Smyth, and S. P. Langdon Insulin-like Growth Factor Binding Proteins IGFBP3, IGFBP4, and IGFBP5 Predict Endocrine Responsiveness in Patients with Ovarian Cancer Clin. Cancer Res., March 1, 2007; 13(5): 1438 - 1444. [Abstract] [Full Text] [PDF] |
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K. Pazaitou-Panayiotou, T. Kelesidis, I. Kelesidis, A. Kaprara, J. Blakeman, I. Vainas, A. Mpousoulegas, C. J Williams, and C. Mantzoros Growth hormone-binding protein is directly and IGFBP-3 is inversely associated with risk of female breast cancer Eur. J. Endocrinol., February 1, 2007; 156(2): 187 - 194. [Abstract] [Full Text] [PDF] |
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S. B. Wheatcroft, M. T. Kearney, A. M. Shah, V. A. Ezzat, J. R. Miell, M. Modo, S. C.R. Williams, W. P. Cawthorn, G. Medina-Gomez, A. Vidal-Puig, et al. IGF-Binding Protein-2 Protects Against the Development of Obesity and Insulin Resistance Diabetes, February 1, 2007; 56(2): 285 - 294. [Abstract] [Full Text] [PDF] |
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C. A. Borgono, I. P. Michael, J. L. V. Shaw, L.-Y. Luo, M. C. Ghosh, A. Soosaipillai, L. Grass, D. Katsaros, and E. P. Diamandis Expression and Functional Characterization of the Cancer-related Serine Protease, Human Tissue Kallikrein 14 J. Biol. Chem., January 26, 2007; 282(4): 2405 - 2422. [Abstract] [Full Text] [PDF] |
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C. M A Reijnders, N. Bravenboer, A. M Tromp, M. A Blankenstein, and P. Lips Effect of mechanical loading on insulin-like growth factor-I gene expression in rat tibia J. Endocrinol., January 1, 2007; 192(1): 131 - 140. [Abstract] [Full Text] [PDF] |
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T. Degenhardt, M. Matilainen, K.-H. Herzig, T. W. Dunlop, and C. Carlberg The Insulin-like Growth Factor-binding Protein 1 Gene Is a Primary Target of Peroxisome Proliferator-activated Receptors J. Biol. Chem., December 22, 2006; 281(51): 39607 - 39619. [Abstract] [Full Text] [PDF] |
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C. Chen, R. Freeman, L. F. Voigt, A. Fitzpatrick, S. R. Plymate, and N. S. Weiss Prostate Cancer Risk in Relation to Selected Genetic Polymorphisms in Insulin-like Growth Factor-I, Insulin-like Growth Factor Binding Protein-3, and Insulin-like Growth Factor-I Receptor Cancer Epidemiol. Biomarkers Prev., December 1, 2006; 15(12): 2461 - 2466. [Abstract] [Full Text] [PDF] |
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S. Yakar, N. P. Nunez, P. Pennisi, P. Brodt, H. Sun, L. Fallavollita, H. Zhao, L. Scavo, R. Novosyadlyy, N. Kurshan, et al. Increased Tumor Growth in Mice with Diet-Induced Obesity: Impact of Ovarian Hormones Endocrinology, December 1, 2006; 147(12): 5826 - 5834. [Abstract] [Full Text] [PDF] |
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L. J. Cobb, B. Liu, K.-W. Lee, and P. Cohen Phosphorylation by DNA-Dependent Protein Kinase Is Critical for Apoptosis Induction by Insulin-Like Growth Factor Binding Protein-3. Cancer Res., November 15, 2006; 66(22): 10878 - 10884. [Abstract] [Full Text] [PDF] |
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A L Pierce, M Shimizu, L Felli, P Swanson, and W W Dickhoff Metabolic hormones regulate insulin-like growth factor binding protein-1 mRNA levels in primary cultured salmon hepatocytes; lack of inhibition by insulin. J. Endocrinol., November 1, 2006; 191(2): 379 - 386. [Abstract] [Full Text] [PDF] |
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X. Yan, R. C. Baxter, B. Perbal, and S. M. Firth The Aminoterminal Insulin-Like Growth Factor (IGF) Binding Domain of IGF Binding Protein-3 Cannot Be Functionally Substituted by the Structurally Homologous Domain of CCN3 Endocrinology, November 1, 2006; 147(11): 5268 - 5274. [Abstract] [Full Text] [PDF] |
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F. Prefumo, S. Canini, A. Crovo, D. Pastorino, P. L. Venturini, and P. De Biasio Correlation between first trimester fetal bone length and maternal serum pregnancy-associated plasma protein-A (PAPP-A) Hum. Reprod., November 1, 2006; 21(11): 3019 - 3021. [Abstract] [Full Text] [PDF] |
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Y. Mitsui, S. Mochizuki, T. Kodama, M. Shimoda, T. Ohtsuka, T. Shiomi, M. Chijiiwa, T. Ikeda, M. Kitajima, and Y. Okada ADAM28 Is Overexpressed in Human Breast Carcinomas: Implications for Carcinoma Cell Proliferation through Cleavage of Insulin-like Growth Factor Binding Protein-3. Cancer Res., October 15, 2006; 66(20): 9913 - 9920. [Abstract] [Full Text] [PDF] |
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N. Ben Lagha, D. Seurin, Y. Le Bouc, M. Binoux, A. Berdal, P. Menuelle, and S. Babajko Insulin-Like Growth Factor Binding Protein (IGFBP-1) Involvement in Intrauterine Growth Retardation: Study on IGFBP-1 Overexpressing Transgenic Mice Endocrinology, October 1, 2006; 147(10): 4730 - 4737. [Abstract] [Full Text] [PDF] |
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L. Peng, P. J. Malloy, J. Wang, and D. Feldman Growth Inhibitory Concentrations of Androgens Up-Regulate Insulin-Like Growth Factor Binding Protein-3 Expression via an Androgen Response Element in LNCaP Human Prostate Cancer Cells Endocrinology, October 1, 2006; 147(10): 4599 - 4607. [Abstract] [Full Text] [PDF] |
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Y. Ning, A. G. P. Schuller, S. Bradshaw, P. Rotwein, T. Ludwig, J. Frystyk, and J. E. Pintar Diminished Growth and Enhanced Glucose Metabolism in Triple Knockout Mice Containing Mutations of Insulin-Like Growth Factor Binding Protein-3, -4, and -5 Mol. Endocrinol., September 1, 2006; 20(9): 2173 - 2186. [Abstract] [Full Text] [PDF] |
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A. Jasinska, Z. Strakova, M. Szmidt, and A. T. Fazleabas Human Chorionic Gonadotropin and Decidualization in Vitro Inhibits Cytochalasin-D-Induced Apoptosis in Cultured Endometrial Stromal Fibroblasts Endocrinology, September 1, 2006; 147(9): 4112 - 4121. [Abstract] [Full Text] [PDF] |
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J. L. Martin and S. Jambazov Insulin-Like Growth Factor Binding Protein-3 in Extracellular Matrix Stimulates Adhesion of Breast Epithelial Cells and Activation of p44/42 Mitogen-Activated Protein Kinase Endocrinology, September 1, 2006; 147(9): 4400 - 4409. [Abstract] [Full Text] [PDF] |
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T. Sitar, G. M. Popowicz, I. Siwanowicz, R. Huber, and T. A. Holak Structural basis for the inhibition of insulin-like growth factors by insulin-like growth factor-binding proteins PNAS, August 29, 2006; 103(35): 13028 - 13033. [Abstract] [Full Text] [PDF] |
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N. Bhattacharyya, K. Pechhold, H. Shahjee, G. Zappala, C. Elbi, B. Raaka, M. Wiench, J. Hong, and M. M. Rechler Nonsecreted Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) Can Induce Apoptosis in Human Prostate Cancer Cells by IGF-independent Mechanisms without Being Concentrated in the Nucleus J. Biol. Chem., August 25, 2006; 281(34): 24588 - 24601. [Abstract] [Full Text] [PDF] |
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K. W Frommer, K. Reichenmiller, B. S Schutt, A. Hoeflich, M. B Ranke, G. Dodt, and M. W Elmlinger IGF-independent effects of IGFBP-2 on the human breast cancer cell line Hs578T. J. Mol. Endocrinol., August 1, 2006; 37(1): 13 - 23. [Abstract] [Full Text] [PDF] |
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R. Rajgopal, M. Butcher, J. I. Weitz, and S. G. Shaughnessy Heparin Synergistically Enhances Interleukin-11 Signaling through Up-regulation of the MAPK Pathway J. Biol. Chem., July 28, 2006; 281(30): 20780 - 20787. [Abstract] [Full Text] [PDF] |
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A. Marchand, C. Tomkiewicz, L. Magne, R. Barouki, and M. Garlatti Endoplasmic Reticulum Stress Induction of Insulin-like Growth Factor-binding Protein-1 Involves ATF4 J. Biol. Chem., July 14, 2006; 281(28): 19124 - 19133. [Abstract] [Full Text] [PDF] |
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B. A. Maddux, A. Chan, L. J. Mandarino, I. D. Goldfine, and E. A. De Filippis IGF-Binding Protein-1 Levels Are Related to Insulin-Mediated Glucose Disposal and Are a Potential Serum Marker of Insulin Resistance Diabetes Care, July 1, 2006; 29(7): 1535 - 1537. [Abstract] [Full Text] [PDF] |
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