This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Resnicoff, M. Articles by Baserga, R. Search for Related Content PubMed PubMed Citation Articles by Resnicoff, M. Articles by Baserga, R.

Correlation between Apoptosis, Tumorigenesis, and Levels of Insulin-like Growth Factor I Receptors¹

Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania

We have investigated whether there is a quantitative relationship between the insulin-like growth factor I receptor (IGF-IR), the extent of apoptosis in vivo, and tumorigenesis. C6 rat glioblastoma cells were treated with increasing concentrations of antisense oligodeoxynucleotides to the IGF-IR RNA. The extent of apoptosis in vivo is correlated to the decrease in IGF-IR levels and, in turn, tumorigenesis in nude mice is correlated to the fraction of surviving cells. In syngeneic rats, a host response leads to complete inhibition of tumorigenesis. These findings establish, for the first time on a quantitative basis, the relationship between IGF-IR levels and the extent of apoptosis, as well as the relationship between the initial apoptotic event and the time of appearance of transplantable tumors.

¹ This work has been supported by NIH Grants 33694 and CA 53484 and by the Edna McConnell Clark Foundation.

² To whom requests for reprints should be addressed, at Jefferson Cancer Institute, Bluemle Life Sciences Building, 233 South 10th Street, Room 624, Philadelphia, PA 19107-5541.

Received 6/19/95. Accepted 7/20/95.

This article has been cited by other articles:

				U. McDermott, A. J. Iafrate, N. S. Gray, T. Shioda, M. Classon, S. Maheswaran, W. Zhou, H. G. Choi, S. L. Smith, L. Dowell, et al. Genomic Alterations of Anaplastic Lymphoma Kinase May Sensitize Tumors to Anaplastic Lymphoma Kinase Inhibitors Cancer Res., May 1, 2008; 68(9): 3389 - 3395. [Abstract] [Full Text] [PDF]

				R. A. Jones, C. I. Campbell, J. J. Petrik, and R. A. Moorehead Characterization of a Novel Primary Mammary Tumor Cell Line Reveals that Cyclin D1 Is Regulated by the Type I Insulin-Like Growth Factor Receptor Mol. Cancer Res., May 1, 2008; 6(5): 819 - 828. [Abstract] [Full Text] [PDF]

				G. Chandrasekher and D. Sailaja Phosphatidylinositol 3-Kinase (PI-3K)/Akt but Not PI-3K/p70 S6 Kinase Signaling Mediates IGF-1-Promoted Lens Epithelial Cell Survival Invest. Ophthalmol. Vis. Sci., October 1, 2004; 45(10): 3577 - 3588. [Abstract] [Full Text] [PDF]

				S. R. Edmondson, S. P. Thumiger, G. A. Werther, and C. J. Wraight Epidermal Homeostasis: The Role of the Growth Hormone and Insulin-Like Growth Factor Systems Endocr. Rev., December 1, 2003; 24(6): 737 - 764. [Abstract] [Full Text] [PDF]

				A. Hongo, H. Kuramoto, Y. Nakamura, K. Hasegawa, K. Nakamura, J. Kodama, and Y. Hiramatsu Antitumor Effects of a Soluble Insulin-Like Growth Factor I Receptor in Human Ovarian Cancer Cells: Advantage of Recombinant Protein Administration in Vivo Cancer Res., November 15, 2003; 63(22): 7834 - 7839. [Abstract] [Full Text] [PDF]

				R. G. Dean, L. A. Bach, and L. M. Burrell Upregulation of Cardiac Insulin-like Growth Factor-I Receptor by ACE Inhibition After Myocardial Infarction: Potential Role in Remodeling J. Histochem. Cytochem., June 1, 2003; 51(6): 831 - 839. [Abstract] [Full Text] [PDF]

				C L Chernicky, H Tan, L Yi, J R L. de Mola, and J Ilan Treatment of murine breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor decreases the level of plasminogen activator transcripts, inhibits cell growth in vitro, and reduces tumorigenesis in vivo Mol. Pathol., April 1, 2002; 55(2): 102 - 109. [Abstract] [Full Text] [PDF]

				K. Hensen, I. C. C. Van Valckenborgh, K. Kas, W. J. M. Van de Ven, and M. L. Voz The Tumorigenic Diversity of the Three PLAG Family Members Is Associated with Different DNA Binding Capacities Cancer Res., March 1, 2002; 62(5): 1510 - 1517. [Abstract] [Full Text] [PDF]

				L. Wang, X. Ma, L.-C. C. Yeh, and M. L. Adamo Differential Regulation of IGF-Binding Protein Gene Expression by cAMP in Rat C6 Glioma Cells Endocrinology, September 1, 2001; 142(9): 3917 - 3925. [Abstract] [Full Text] [PDF]

				L. Wang and M. L. Adamo Cyclic Adenosine 3',5'-Monophosphate Inhibits Insulin-Like Growth Factor I Gene Expression in Rat Glioma Cell Lines: Evidence for Regulation of Transcription and Messenger Ribonucleic Acid Stability Endocrinology, July 1, 2001; 142(7): 3041 - 3050. [Abstract] [Full Text] [PDF]

				K. Reiss, X. Tu, G. Romano, F. Peruzzi, J. Y. Wang, and R. Baserga Intracellular Association of a Mutant Insulin-like Growth Factor Receptor with Endogenous Receptors Clin. Cancer Res., July 1, 2001; 7(7): 2134 - 2144. [Abstract] [Full Text] [PDF]

				D. W. Andrews, M. Resnicoff, A. E. Flanders, L. Kenyon, M. Curtis, G. Merli, R. Baserga, G. Iliakis, and R. D. Aiken Results of a Pilot Study Involving the Use of an Antisense Oligodeoxynucleotide Directed Against the Insulin-Like Growth Factor Type I Receptor in Malignant Astrocytomas J. Clin. Oncol., April 15, 2001; 19(8): 2189 - 2200. [Abstract] [Full Text] [PDF]

				R Issa, E Williams, N Trim, T Kendall, M J P Arthur, J Reichen, R C Benyon, and J P Iredale Apoptosis of hepatic stellate cells: involvement in resolution of biliary fibrosis and regulation by soluble growth factors Gut, April 1, 2001; 48(4): 548 - 557. [Abstract] [Full Text] [PDF]

				D. Le Roith, C. Bondy, S. Yakar, J.-L. Liu, and A. Butler The Somatomedin Hypothesis: 2001 Endocr. Rev., February 1, 2001; 22(1): 53 - 74. [Abstract] [Full Text]

				L. Wang and M. L. Adamo Cell Density Influences Insulin-Like Growth Factor I Gene Expression in a Cell Type-Specific Manner Endocrinology, July 1, 2000; 141(7): 2481 - 2489. [Abstract] [Full Text] [PDF]

				H. M. Khandwala, I. E. McCutcheon, A. Flyvbjerg, and K. E. Friend The Effects of Insulin-Like Growth Factors on Tumorigenesis and Neoplastic Growth Endocr. Rev., June 1, 2000; 21(3): 215 - 244. [Abstract] [Full Text]

				C Berry and A.L Clark Catabolism in chronic heart failure Eur. Heart J., April 1, 2000; 21(7): 521 - 532. [PDF]

				A. Vogt, A. S. Wang, C. S. Johnson, J. P. Fabisiak, P. Wipf, and J. S. Lazo In Vivo Antitumor Activity and Induction of Insulin-Like Growth Factor-1-Resistant Apoptosis by SC-alpha alpha delta 9 J. Pharmacol. Exp. Ther., February 1, 2000; 292(2): 530 - 537. [Abstract] [Full Text]

				F. Peruzzi, M. Prisco, M. Dews, P. Salomoni, E. Grassilli, G. Romano, B. Calabretta, and R. Baserga Multiple Signaling Pathways of the Insulin-Like Growth Factor 1 Receptor in Protection from Apoptosis Mol. Cell. Biol., October 1, 1999; 19(10): 7203 - 7215. [Abstract] [Full Text] [PDF]

				Y. Xie, B. Skytting, G. Nilsson, B. Brodin, and O. Larsson Expression of Insulin-like Growth Factor-1 Receptor in Synovial Sarcoma: Association with an Aggressive Phenotype Cancer Res., August 1, 1999; 59(15): 3588 - 3591. [Abstract] [Full Text] [PDF]

				H. Hirano, M. B. S. Lopes, E. R. Laws Jr., T. Asakura, M. Goto, J. E. Carpenter, L. R. Karns, and S. R. VandenBerg Insulin-like growth factor-1 content and pattern of expression correlates with histopathologic grade in diffusely infiltrating astrocytomas Neuro-oncol, April 1, 1999; 1(2): 109 - 119. [Abstract] [PDF]

				A. Frustaci, C. Chimenti, M. Setoguchi, S. Guerra, S. Corsello, F. Crea, A. Leri, J. Kajstura, P. Anversa, and A. Maseri Cell Death in Acromegalic Cardiomyopathy Circulation, March 23, 1999; 99(11): 1426 - 1434. [Abstract] [Full Text] [PDF]

				H. Hosoi, M. B. Dilling, T. Shikata, L. N. Liu, L. Shu, R. A. Ashmun, G. S. Germain, R. T. Abraham, and P. J. Houghton Rapamycin Causes Poorly Reversible Inhibition of mTOR and Induces p53-independent Apoptosis in Human Rhabdomyosarcoma Cells Cancer Res., February 1, 1999; 59(4): 886 - 894. [Abstract] [Full Text] [PDF]

				A. Leri, Y. Liu, P. P. Claudio, J. Kajstura, X. Wang, S. Wang, P. Kang, A. Malhotra, and P. Anversa Insulin-Like Growth Factor-1 Induces Mdm2 and Down-Regulates p53, Attenuating the Myocyte Renin-Angiotensin System and Stretch-Mediated Apoptosis Am. J. Pathol., February 1, 1999; 154(2): 567 - 580. [Abstract] [Full Text] [PDF]

				J. Niebauer, C.-D. Pflaum, A. L. Clark, C. J. Strasburger, J. Hooper, P. A. Poole-Wilson, A. J. S. Coats, and S. D. Anker Deficient insulin-like growth factor I in chronic heart failure predicts altered body composition, anabolic deficiency, cytokine and neurohormonal activation J. Am. Coll. Cardiol., August 1, 1998; 32(2): 393 - 397. [Abstract] [Full Text] [PDF]

				M. Resnicoff, B. Valentinis, D. Herbert, D. Abraham, P. D. Friesen, E. S. Alnemri, and R. Baserga The Baculovirus Anti-apoptotic p35 Protein Promotes Transformation of Mouse Embryo Fibroblasts J. Biol. Chem., April 24, 1998; 273(17): 10376 - 10380. [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. A. Toretsky, T. Kalebic, V. Blakesley, D. LeRoith, and L. J. Helman The Insulin-like Growth Factor-I Receptor Is Required for EWS/FLI-1 Transformation of Fibroblasts J. Biol. Chem., December 5, 1997; 272(49): 30822 - 30827. [Abstract] [Full Text] [PDF]

				A. Morrione, B. Valentinis, M. Resnicoff, S.-q. Xu, and R. Baserga The Role of mGrb10alpha in Insulin-like Growth Factor I-mediated Growth J. Biol. Chem., October 17, 1997; 272(42): 26382 - 26387. [Abstract] [Full Text] [PDF]

				S G Kennedy, A J Wagner, S D Conzen, J Jordan, A Bellacosa, P N Tsichlis, and N Hay The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes & Dev., March 15, 1997; 11(6): 701 - 713. [Abstract] [PDF]

				T. Bui, C. Kuo, P. Rotwein, and D. S. Straus Prostaglandin A2 Specifically Represses Insulin-Like Growth Factor-I Gene Expression in C6 Rat Glioma Cells Endocrinology, March 1, 1997; 138(3): 985 - 993. [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]

				C. E. H. Stewart and P. Rotwein Insulin-like Growth Factor-II Is an Autocrine Survival Factor for Differentiating Myoblasts J. Biol. Chem., May 10, 1996; 271(19): 11330 - 11338. [Abstract] [Full Text] [PDF]

				S. Peretz, R. Jensen, R. Baserga, and P. M. Glazer ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response PNAS, February 13, 2001; 98(4): 1676 - 1681. [Abstract] [Full Text] [PDF]