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The Insulin-like Growth Factor I Receptor: A Key to Tumor Growth?

Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Philadelphia 19107

The insulin-like growth factor I receptor (IGF-IR) belongs to the family of transmembrane tyrosine kinase receptors, like the receptors for platelet-derived growth factor, the epidermal growth factor, insulin, and others.

Genetic evidence has shown that the IGF-IR is required for optimal growth in vitro and in vivo. Even more important, however, have been recent findings from several laboratories clearly showing that the IGF-IR is an absolute requirement for the establishment and maintenance of the transformed phenotype, both in vivo and in vitro and in several cell types. These findings indicate that the IGF-IR plays a central role in the mechanism of transformation and, as such, could be a preferred target for therapeutic interventions.

Received 10/21/94. Accepted 11/ 8/94.

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				Z.-D. Xu, L. Oey, S. Mohan, M. H. Kawachi, N.-S. Lee, J. J. Rossi, and Y. Fujita-Yamaguchi Hammerhead Ribozyme-Mediated Cleavage of the Human Insulin-Like Growth Factor-II Ribonucleic Acid in Vitro and in Prostate Cancer Cells Endocrinology, May 1, 1999; 140(5): 2134 - 2144. [Abstract] [Full Text]

				H. Yoshimoto, H. Ishihara, A. Ohtsuru, K. Akino, R. Murakami, H. Kuroda, H. Namba, M. Ito, T. Fujii, and S. Yamashita Overexpression of Insulin-Like Growth Factor-1 (IGF-I) Receptor and the Invasiveness of Cultured Keloid Fibroblasts Am. J. Pathol., March 1, 1999; 154(3): 883 - 889. [Abstract] [Full Text] [PDF]

				H. Yu, M. R. Spitz, J. Mistry, J. Gu, W. K. Hong, and X. Wu Plasma Levels of Insulin-Like Growth Factor-I and Lung Cancer Risk: a Case-Control Analysis J Natl Cancer Inst, January 20, 1999; 91(2): 151 - 156. [Abstract] [Full Text] [PDF]

				G. R. Devi, J. C. Byrd, D. H. Slentz, and R. G. MacDonald An Insulin-Like Growth Factor II (IGF-II) Affinity-Enhancing Domain Localized within Extracytoplasmic Repeat 13 of the IGF-II/Mannose 6-Phosphate Receptor Mol. Endocrinol., November 1, 1998; 12(11): 1661 - 1672. [Abstract] [Full Text]

				A. Casamassima and E. Rozengurt Insulin-like Growth Factor I Stimulates Tyrosine Phosphorylation of p130Cas, Focal Adhesion Kinase, and Paxillin. ROLE OF PHOSPHATIDYLINOSITOL 3'-KINASE AND FORMATION OF A p130Cas·Crk COMPLEX J. Biol. Chem., October 2, 1998; 273(40): 26149 - 26156. [Abstract] [Full Text] [PDF]

				W. Li, Y.-X. Jiang, J. Zhang, L. Soon, L. Flechner, V. Kapoor, J. H. Pierce, and L.-H. Wang Protein Kinase C-delta Is an Important Signaling Molecule in Insulin-Like Growth Factor I Receptor-Mediated Cell Transformation Mol. Cell. Biol., October 1, 1998; 18(10): 5888 - 5898. [Abstract] [Full Text]

				Y. Okajima, I. Matsumura, T. Nishiura, K. Hashimoto, H. Yoshida, J. Ishikawa, H. Wakao, A. Yoshimura, Y. Kanakura, Y. Tomiyama, et al. Insulin-like Growth Factor-I Augments Erythropoietin-induced Proliferation through Enhanced Tyrosine Phosphorylation of STAT5 J. Biol. Chem., September 4, 1998; 273(36): 22877 - 22883. [Abstract] [Full Text] [PDF]

				S. E. Damon, L. Maddison, J. L. Ware, and S. R. Plymate Overexpression of an Inhibitory Insulin-Like Growth Factor Binding Protein (IGFBP), IGFBP-4, Delays Onset of Prostate Tumor Formation Endocrinology, August 1, 1998; 139(8): 3456 - 3464. [Abstract] [Full Text] [PDF]

				J. E. Boehm, O. V. Chaika, and R. E. Lewis Anti-apoptotic Signaling by a Colony-stimulating Factor-1 Receptor/Insulin Receptor Chimera with a Juxtamembrane Deletion J. Biol. Chem., March 20, 1998; 273(12): 7169 - 7176. [Abstract] [Full Text] [PDF]

				C. Ohlsson, N. Kley, H. Werner, and D. LeRoith p53 Regulates Insulin-Like Growth Factor-I (IGF-I) Receptor Expression and IGF-I-Induced Tyrosine Phosphorylation in an Osteosarcoma Cell Line: Interaction between p53 and Sp1 Endocrinology, March 1, 1998; 139(3): 1101 - 1107. [Abstract] [Full Text] [PDF]

				J.-L. Liu, V. A. Blakesley, J. S. Gutkind, and D. LeRoith The Constitutively Active Mutant Galpha 13 Transforms Mouse Fibroblast Cells Deficient in Insulin-like Growth Factor-I Receptor J. Biol. Chem., November 21, 1997; 272(47): 29438 - 29441. [Abstract] [Full Text] [PDF]

				M. Karas, M. Danilenko, D. Fishman, D. LeRoith, J. Levy, and Y. Sharoni Membrane-associated Insulin-like Growth Factor-binding Protein-3 Inhibits Insulin-like Growth Factor-I-induced Insulin-like Growth Factor-I Receptor Signaling in Ishikawa Endometrial Cancer Cells J. Biol. Chem., June 27, 1997; 272(26): 16514 - 16520. [Abstract] [Full Text] [PDF]

				R. Baserga Editorial: The Path Less Traveled By Endocrinology, June 1, 1997; 138(6): 2217 - 2218. [Full Text] [PDF]

				F. L. Garrouste, M. M. Remacle-Bonnet, M. M.-A. Lehmann, J. L. Marvaldi, and G. J. Pommier Up-Regulation of Insulin/Insulin-Like Growth Factor-I Hybrid Receptors during Differentiation of HT29-D4 Human Colonic Carcinoma Cells Endocrinology, May 1, 1997; 138(5): 2021 - 2032. [Abstract] [Full Text] [PDF]

				R. Clark The Somatogenic Hormones and Insulin-Like Growth Factor-1: Stimulators of Lymphopoiesis and Immune Function Endocr. Rev., April 1, 1997; 18(2): 157 - 179. [Abstract] [Full Text]

				S. R. Plymate, V. L. Bae, L. Maddison, L. S. Quinn, and J. L. Ware Reexpression of the Type 1 Insulin-Like Growth Factor Receptor Inhibits the Malignant Phenotype of Simian Virus 40 T Antigen Immortalized Human Prostate Epithelial Cells Endocrinology, April 1, 1997; 138(4): 1728 - 1735. [Abstract] [Full Text] [PDF]

				C. Huang, P. C. Schmid, W.-Y. Ma, H. H.O. Schmid, and Z. Dong Phosphatidylinositol-3 Kinase Is Necessary for 12-O-Tetradecanoylphorbol-13-acetate-induced Cell Transformation and Activated Protein 1Activation J. Biol. Chem., February 14, 1997; 272(7): 4187 - 4194. [Abstract] [Full Text] [PDF]

				J. E. Peterson, G. Kulik, T. Jelinek, C. W.M. Reuter, J. A. Shannon, and M. J. Weber Src Phosphorylates the Insulin-like Growth Factor Type I Receptor on the Autophosphorylation Sites. REQUIREMENT FOR TRANSFORMATION BY src J. Biol. Chem., December 6, 1996; 271(49): 31562 - 31571. [Abstract] [Full Text] [PDF]

				R. S. Warren, H. Yuan, M. R. Matli, N. Ferrara, and D. B. Donner Induction of Vascular Endothelial Growth Factor by Insulin-like Growth Factor 1in Colorectal Carcinoma J. Biol. Chem., November 15, 1996; 271(46): 29483 - 29488. [Abstract] [Full Text] [PDF]

				S. Tanaka, T. Ito, and J. R. Wands Neoplastic Transformation Induced by Insulin Receptor Substrate-1 Overexpression Requires an Interaction with Both Grb2 and Syp Signaling Molecules J. Biol. Chem., June 14, 1996; 271(24): 14610 - 14616. [Abstract] [Full Text] [PDF]

				S. Li, M. Resnicoff, and R. Baserga Effect of Mutations at Serines 1280-1283 on the Mitogenic and Transforming Activities of the Insulin-like Growth Factor I Receptor J. Biol. Chem., May 24, 1996; 271(21): 12254 - 12260. [Abstract] [Full Text] [PDF]

				R. Zarrilli, M. Romano, S. Pignata, S. Casola, C. B. Bruni, and A. M. Acquaviva Constitutive Insulin-like Growth Factor-II Expression Interferes with the Enterocyte-like Differentiation of CaCo-2 Cells J. Biol. Chem., April 5, 1996; 271(14): 8108 - 8114. [Abstract] [Full Text] [PDF]

				H. Huynh, X. Yang, and M. Pollak Estradiol and Antiestrogens Regulate a Growth Inhibitory Insulin-like Growth Factor Binding Protein 3 Autocrine Loop in Human Breast Cancer Cells J. Biol. Chem., January 12, 1996; 271(2): 1016 - 1021. [Abstract] [Full Text] [PDF]

				B. Xu, V. G. Bird, and W. T. Miller Substrate Specificities of the Insulin and Insulin-like Growth Factor 1 Receptor Tyrosine Kinase Catalytic Domains J. Biol. Chem., December 15, 1995; 270(50): 29825 - 29830. [Abstract] [Full Text] [PDF]

				C. S. Zong, J. Chan, D. E. Levy, C. Horvath, H. B. Sadowski, and L.-H. Wang Mechanism of STAT3 Activation by Insulin-like Growth Factor I Receptor J. Biol. Chem., May 12, 2000; 275(20): 15099 - 15105. [Abstract] [Full Text] [PDF]

				C. Miele, J. J. Rochford, N. Filippa, S. Giorgetti-Peraldi, and E. Van Obberghen Insulin and Insulin-like Growth Factor-I Induce Vascular Endothelial Growth Factor mRNA Expression via Different Signaling Pathways J. Biol. Chem., July 7, 2000; 275(28): 21695 - 21702. [Abstract] [Full Text] [PDF]

				S. Giraud, A. Greco, M. Brink, J.-J. Diaz, and P. Delafontaine Translation Initiation of the Insulin-like Growth Factor I Receptor mRNA Is Mediated by an Internal Ribosome Entry Site J. Biol. Chem., February 16, 2001; 276(8): 5668 - 5675. [Abstract] [Full Text] [PDF]

				M. J. Horney, C. A. Evangelista, and S. A. Rosenzweig Synthesis and Characterization of Insulin-like Growth Factor (IGF)-1 Photoprobes Selective for the IGF-binding Proteins (IGFBPs). PHOTOAFFINITY LABELING OF THE IGF-BINDING DOMAIN ON IGFBP-2 J. Biol. Chem., January 19, 2001; 276(4): 2880 - 2889. [Abstract] [Full Text] [PDF]

				A. Yam, T. Hyun, and W. Li Characterization of Insulin-like Growth Factor I (IGF-I) Receptor Mutants for Their Effects on IGF-I- and Interleukin 4-mediated DNA Synthesis of 32D Cells J. Biol. Chem., June 22, 2001; 276(26): 24409 - 24413. [Abstract] [Full Text] [PDF]