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DOI: 10.1055/s-2004-814142
The Insulin-like Growth Factors and Insulin-signalling Systems: An Appealing Target for Breast Cancer Therapy?
Publication History
Received 20 September 2003
Accepted after Revision 11 November 2003
Publication Date:
07 January 2004 (online)
![](https://www.thieme-connect.de/media/hmr/20031112/lookinside/thumbnails/10.1055-s-2004-814142-1.jpg)
Abstract
There is compelling evidence from epidemiological studies in humans, as well as in vitro and in vivo experimental observations including transgenic animal models, for a role of the IGF/insulin signalling system in cancer tumourigenesis. In this review focused on breast cancer, we review the experimental evidence, discuss the cellular and molecular mechanisms of tumourigenicity by the IGFs and insulin and various possible therapeutic strategies based on the mechanisms discussed.
Key words
Insulin - IGF-I - Cancer
References
- 1 Khandwala H M, McCutcheon I E, Flyvbjerg A, Friend K E. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev. 2000; 21 215-244
- 2 LeRoith D, Roberts C T. The insulin-like growth factor system and cancer. Cancer Lett. 2003; 195 127-137
- 3 Robinson D R, Wu Y M, Lin S F. The protein tyrosine kinase family of the human genome. Oncogene. 2000; 19 5548-5557
- 4 Levitzki A. Tyrosine kinases as targets for cancer therapy. Eur J Cancer. 2002; 38 Suppl 5 S11-S18
- 5 Drevs J, Medinger M, Schmidt-Gersbach C, Weber R, Unger C. Receptor tyrosine kinases: the main targets for new anticancer therapy. Curr Drug Targets. 2003; 4 113-121
- 6 Traxler P. Tyrosine kinases as targets in cancer therapy - successes and failures. Expert Opin Ther Targets. 2003; 7 215-234
- 7 Zwick E, Bange J, Ullrich A. Receptor tyrosine kinases as targets for anticancer drugs. Trends Mol Med. 2002; 8 17-23
- 8 De Meyts P, Whittaker J. Structural biology of insulin and IGF1 receptors: implications for drug design. Nat Rev Drug Discov. 2002; 1 769-783
- 9 De Meyts P. The structural basis of insulin and insulin-like growth factor-I (IGF-I) receptor binding and negative cooperativity, and its relevance to mitogenic versus metabolic signaling. Diabetologia. 1994; 37 (Suppl 2) S135-S148
- 10 Frasca F, Pandini G, Scalia P, Sciacca L, Mineo R, Costantino A, Goldfine I D, Belfiore A, Vigneri R. Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells. Mol Cell Biol. 1999; 19 3278-3288
- 11 Saltiel A R, Pessin J E. Insulin signaling pathways in time and space. Trends Cell Biol. 2002; 12 65-71
- 12 Wang L H, Lin B, Jong S MJ, Dixon D, Ellis L, Roth R A, Rutter W J. Activation of the transforming potential of the human insulin receptor gene. Proc Natl Acad Sci USA. 1987; 84 5725-5729
- 13 Urso B, Ilondo M M, Holst P A, Christoffersen C T, Ouwens M, Giorgetti S, van Obberghen E, Naor D, Tornqvist H, De Meyts P. IRS-4 mediated mitogenic signalling by insulin and growth hormone in LB cells, a murine T-cell lymphoma devoid of IGF-I receptors. Cell Signal. 2003; 15 385-394
- 14 Kaaks R. Nutrition, hormones, and breast cancer: is insulin the missing link?. Cancer Causes Control. 1996; 7 605-625
- 15 Hadsell D L, Bonnette S G, Lee A V. Genetic manipulation of the IGF-I axis to regulate mammary gland development and function. J Dairy Sci. 2002; 85 365-377
- 16 Ruan W, Kleinberg D L. Insulin-like growth factor I is essential for terminal end bud formation and ductal morphogenesis during mammary development. Endocrinology. 1999; 140 5075-5081
- 17 Clevenger C V, Furth P A, Hankinson S E, Schuler L A. The role of prolactin in mammary carcinoma. Endocr Rev. 2003; 24 1-27
- 18 Grimm S L, Seagroves T N, Kabotyanski E B, Hovey R C, Vonderhaar B K, Lydon J P, Miyoshi K, Hennighausen L, Ormandy C J, Lee A V, Stull M A, Wood T L, Rosen J M. Disruption of steroid and prolactin receptor patterning in the mammary gland correlates with a block in lobuloalveolar development. Mol Endocrinol. 2002; 16 2675-2691
- 19 Bagheri-Yarmand R, Vadlamudi R K, Kumar R. Activating transcription factor 4 overexpression inhibits proliferation and differentiation of mammary epithelium resulting in impaired lactation and accelerated involution. J Biol Chem. 2003; 278 17421-17429
- 20 Dupont J, Renou J P, Shani M, Hennighausen L, LeRoith D. PTEN overexpression suppresses proliferation and differentiation and enhances apoptosis of the mouse mammary epithelium. J Clin Invest. 2002; 110 815-825
- 21 Woelfle J, Billiard J, Rotwein P. Acute control of insulin-like growth factor-I gene transcription by growth hormone through Stat5b. J Biol Chem. 2003; 278 22696-22702
- 22 Wu Y, Cui K, Miyoshi K, Hennighausen L, Green J E, Setser J, LeRoith D, Yakar S. Reduced circulating insulin-like growth factor I levels delay the onset of chemically and genetically induced mammary tumors. Cancer Res. 2003; 63 4384-4388
- 23 Hamelers I H, Steenbergh P H. Interactions between estrogen and insulin-like growth factor signaling pathways in human breast tumor cells. Endocr Relat Cancer. 2003; 10 331-345
- 24 Solomon C S, Goalstone M L. Dominant negative alpha-subunit of FTase inhibits effects of insulin and IGF-I in MCF-7 cells. Biochem Biophys Res Commun. 2002; 291 458-465
- 25 Liu Y, Ludes-Meyers J, Zhang Y, Munoz-Medellin D, Kim H T, Lu C, Ge G, Schiff R, Hilsenbeck S G, Osborne C K, Brown P H. Inhibition of AP-1 transcription factor causes blockade of multiple signal transduction pathways and inhibits breast cancer growth. Oncogene. 2002; 21 7680-7689
- 26 Ewton D Z, Kansra S, Lim S, Friedman E. Insulin-like growth factor-I has a biphasic effect on colon carcinoma cells through transient inactivation of forkhead1, initially mitogenic, then mediating growth arrest and differentiation. Int J Cancer. 2002; 98 665-673
- 27 Dupont J, Dunn S E, Barrett J C, LeRoith D. Microarray analysis and identification of novel molecules involved in insulin-like growth factor-1 receptor signaling and gene expression. Recent Prog Horm Res. 2003; 58 325-342
- 28 Reiss K, Wang J Y, Romano G, Furnari F B, Cavenee W K, Morrione A, Tu X, Baserga R. IGF-I receptor signaling in a prostatic cancer cell line with a PTEN mutation. Oncogene. 2000; 19 2687-2694
- 29 Kluska A, Skasko E, Paszko Z. Insulin-like growth factor-I receptor and its relationships to receptors for oestrogen, progesterone and epidermal growth factor in primary breast carcinoma in women. Adv Clin Exp Med. 2002; 11 429-435
- 30 Carroll J S, Lynch D K, Swarbrick A, Renoir J M, Sarcevic B, Daly R J, Musgrove E A, Sutherland R L. p27(Kip1) induces quiescence and growth factor insensitivity in tamoxifen-treated breast cancer cells. Cancer Res. 2003; 63 4322-4326
- 31 Cui X, Zhang P, Deng W, Oesterreich S, Lu Y, Mills G B, Lee A V. Insulin-like growth factor-I inhibits progesterone receptor expression in breast cancer cells via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathway: Progesterone receptor as a potential indicator of growth factor activity in breast cancer. Mol Endocrinol. 2003; 17 575-588
- 32 Chakravarti A, Loeffler J S, Dyson N J. Insulin-like growth factor receptor I mediates resistance to anti-epidermal growth factor receptor therapy in primary human glioblastoma cells through continued activation of phosphoinositide 3-kinase signaling. Cancer Res. 2002; 62 200-207
- 33 Gilmore A P, Valentijn A J, Wang P, Ranger A M, Bundred N, O'Hare M J, Wakeling A, Korsmeyer S J, Streuli C H. Activation of BAD by therapeutic inhibition of epidermal growth factor receptor and transactivation by insulin-like growth factor receptor. J Biol Chem. 2002; 277 27643-27650
- 34 Zelzer E, Levy Y, Kahana C, Shilo B Z, Rubinstein M, Cohen B. Insulin induces transcription of target genes through the hypoxia-inducible factor HIF-1alpha/ARNT. EMBO J. 1998; 17 5085-5094
- 35 Hirtenlehner K, Pec M, Kubista E, Singer C F. Influences of stroma-derived growth factors on the cytokine expression pattern of human breast cancer cell lines. Arch Gynecol Obstet. 2002; 266 108-113
- 36 Guvakova M A, Surmacz E. The activated insulin-like growth factor I receptor induces depolarization in breast epithelial cells characterized by actin filament disassembly and tyrosine dephosphorylation of FAK, Cas, and paxillin. Exp Cell Res. 1999; 251 244-255
- 37 Hermanto U, Zong C S, Li W, Wang L H. RACK1, an insulin-like growth factor I (IGF-I) receptor-interacting protein, modulates IGF-I-dependent integrin signaling and promotes cell spreading and contact with extracellular matrix. Mol Cell Biol. 2002; 22 2345-2365
- 38 Dunn S E, Torres J V, Nihei N, Barrett J C. The insulin-like growth factor-1 elevates urokinase-type plasminogen activator-1 in human breast cancer cells: A new avenue for breast cancer therapy. Mol Carcinog. 2000; 27 10-17
- 39 Bartucci M, Morelli C, Mauro L, Ando S, Surmacz E. Differential insulin-like growth factor I receptor signaling and function in estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cells. Cancer Research. 2001; 61 6747-6754
- 40 Pennisi P A, Barr V, Nunez N P, Stannard B, LeRoith D. Reduced expression of insulin-like growth factor I receptors in MCF-7 breast cancer cells leads to a more metastatic phenotype. Cancer Res. 2002; 62 6529-6537
- 41 Sperandio S, De Belle I, Bredesen D E. An alternative, nonapoptotic form of programmed cell death. Proc Natl Acad Sci USA. 2000; 97 14376-14381
- 42 Valentinis B, Morrione A, Peruzzi F, Prisco M, Reiss K, Baserga R. Anti-apoptotic signaling of the IGF-I receptor in fibroblasts following loss of matrix adhesion. Oncogene. 1999; 18 1827-1836
- 43 Mitsiades C S, Mitsiades N, Poulaki V, Schlossman R, Akiyama M, Chauhan D, Hideshima T, Treon S P, Munshi N C, Richardson P G, Anderson K C. Activation of NF-kappaB and upregulation of intracellular anti-apoptotic proteins via the IGF-1/Akt signaling in human multiple myeloma cells: therapeutic implications. Oncogene. 2002; 21 5673-5683
- 44 Tseng Y, Ueki K, Kriauciunas K M, Kahn C R. Differential roles of insulin receptor substrates in the anti-apoptotic function of insulin-like growth factor-1 and insulin. J Biol Chem. 2002; 277 31 601-31 611
- 45 Galvan V, Logvinova A, Sperandio S, Ichijo H, Bredesen D E. Type 1 insulin-like growth factor receptor (IGF-IR) signaling inhibits apoptosis signal-regulating kinase 1 (ASK1). J Biol Chem. 2003; 278 13325-13332
- 46 Kim A H, Sasaki T, Chao M V. JNK-interacting Protein 1 Promotes Akt1 Activation. J Biol Chem. 2003; 278 29830-29836
- 47 Heron-Milhavet L, LeRoith D. Insulin-like growth factor I induces MDM2-dependent degradation of p53 via the p38 MAPK pathway in response to DNA damage. J Biol Chem. 2002; 277 15600-15606
- 48 Suhara T, Kim H S, Kirshenbaum L A, Walsh K. Suppression of Akt signaling induces Fas ligand expression: involvement of caspase and Jun kinase activation in Akt-mediated Fas ligand regulation. Mol Cell Biol. 2002; 22 680-691
- 49 Gray S G, Ekström T J. The human histone deacetylase family. Exp Cell Res. 2001; 262 75-83
- 50 Harada S, Smith R M, Jarett L. Mechanisms of nuclear translocation of insulin. Cell Biochem Biophys. 1999; 31 307-319
- 51 Mosley A L, Ozcan S. Glucose regulates insulin gene transcription by hyperacetylation of histone h4. J Biol Chem. 2003; 278 19660-19666
- 52 Gray S G, Yakovleva T, Hartmann W, Tally M, Bakalkin G, Ekström T J. IGF-II enhances trichostatin A-induced TGFbeta1 and p21(Waf1,Cip1, sdi1) expression in Hep3B cells. Exp Cell Res. 1999; 253 618-628
- 53 Gray S G, Kytola S, Lui W O, Larsson C, Ekström T J. Modulating IGFBP-3 expression by trichostatin A: potential therapeutic role in the treatment of hepatocellular carcinoma. Int J Mol Med. 2000; 5 33-41
- 54 Recillas-Targa F. DNA Methylation, Chromatin boundaries, and mechanisms of genomic imprinting. Archives of Medical Research. 2002; 33 428-438
- 55 Filippova G N, Qi C F, Ulmer J E, Moore J M, Ward M D, Hu Y J, Loukinov D I, Pugacheva E M, Klenova E M, Grundy P E, Feinberg A P, Cleton-Jansen A M, Moerland E W, Cornelisse C J, Suzuki H, Komiya A, Lindblom A, Dorion-Bonnet F, Neiman P E, Morse H C III, Collins S J, Lobanenkov V V. Tumor-associated zinc finger mutations in the CTCF transcription factor selectively alter its DNA-binding specificity. Cancer Res. 2002; 62 48-52
- 56 Chappell S A, Walsh T, Walker R A, Shaw J A. Loss of heterozygosity at the mannose 6-phosphate insulin-like growth factor 2 receptor gene correlates with poor differentiation in early breast carcinomas. Br J Cancer. 1997; 76 1558-1561
- 57 Chen Z, Ge Y, Landman N, Kang J X. Decreased expression of the mannose 6-phosphate/insulin-like growth factor-II receptor promotes growth of human breast cancer cells. BMC Cancer. 2002; 2 18-26
- 58 Firth S M, Baxter R C. Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev. 2002; 23 824-854
- 59 Tonner E, Barber M C, Allan G J, Beattie J, Webster J, Whitelaw C B, Flint D J. Insulin-like growth factor binding protein-5 (IGFBP-5) induces premature cell death in the mammary glands of transgenic mice. Development. 2002; 129 4547-4557
- 60 Chapman R S, Duff E K, Lourenco P C, Tonner E, Flint D J, Clarke A R, Watson C J. A novel role for IRF-1 as a suppressor of apoptosis. Oncogene. 2000; 19 6386-6391
- 61 Eriksson U, Duc G, Froesch E R, Zapf J. Insulin-like growth factors (IGF) I and II and IGF binding proteins (IGFBPs) in human colostrum/transitory milk during the first week postpartum: comparison with neonatal and maternal serum. Biochem Biophys Res Commun. 1993; 196 267-273
- 62 Sheikh M S, Shao Z M, Hussain A, Clemmons D R, Chen J C, Roberts C T Jr, LeRoith D, Fontana J A. Regulation of insulin-like growth factor-binding-protein-1, 2, 3, 4, 5, and 6: synthesis, secretion, and gene expression in estrogen receptor-negative human breast carcinoma cells. J Cell Physiol. 1993; 155 556-567
- 63 West M, Blanchette C, Dressman H, Huang E, Ishida S, Spang R, Zuzan H, Olson J A Jr, Marks J R, Nevins J R. Predicting the clinical status of human breast cancer by using gene expression profiles. Proc Natl Acad Sci USA. 2001; 98 11462-11467
- 64 Mackay A, Jones C, Dexter T, Silva R L, Bulmer K, Jones A, Simpson P, Harris R A, Jat P S, Neville A M, Reis L F, Lakhani S R, O'Hare M J. cDNA microarray analysis of genes associated with ERBB2 (HER2/neu) overexpression in human mammary luminal epithelial cells. Oncogene. 2003; 22 2680-2688
- 65 Schmid M C, Bisoffi M, Wetterwald A, Gautschi E, Thalmann G N, Mitola S, Bussolino F, Cecchini M G. Insulin-like growth factor binding protein-3 is overexpressed in endothelial cells of mouse breast tumor vessels. Int J Cancer. 2003; 103 577-586
- 66 Zajchowski D A, Bartholdi M F, Gong Y, Webster L, Liu H L, Munishkin A, Beauheim C, Harvey S, Ethier S P, Johnson P H. Identification of gene expression profiles that predict the aggressive behavior of breast cancer cells. Cancer Res. 2001; 61 5168-5178
- 67 Ng E H, Ji C Y, Tan P H, Lin V, Soo K C, Lee K O. Altered serum levels of insulin-like growth-factor binding proteins in breast cancer patients. Ann Surg Oncol. 1998; 5 194-201
- 68 Krajcik R A, Borofsky N D, Massardo S, Orentreich N. Insulin-like growth factor I (IGF-I), IGF-binding proteins, and breast cancer. Cancer Epidemiol Biomarkers Prev. 2002; 11 1566-1573
- 69 Enriori P J, Fischer C R, Gori J R, Etkin A E, Calandra R S, Luthy I A. Augmented serum levels of the IGF-I/IGF-binding protein-3 ratio in pre-menopausal patients with type I breast cysts. Eur J Endocrinol. 2003; 148 177-184
- 70 Sauter E R, Chervoneva I, Diamandis A, Khosravi J M, Litwin S, Diamandis E P. Prostate-specific antigen and insulin-like growth factor binding protein-3 in nipple aspirate fluid are associated with breast cancer. Cancer Detect Prev. 2002; 26 149-157
- 71 Sorlie T, Tibshirani R, Parker J, Hastie T, Marron J S, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou C M, Lonning P E, Brown P O, Borresen-Dale A-L, Botstein D. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003; 100 8418-8423
- 72 Ahr A, Holtrich U, Solbach C, Scharl A, Strebhardt K, Karn T, Kaufmann M. Molecular classification of breast cancer patients by gene expression profiling. J Pathol. 2001; 195 312-320
- 73 van't Veer L J, Dai H, van de Vijver M J, He Y D, Hart A A, Mao M, Peterse H L, van der Kooy K, Marton M J, Witteveen A T, Schreiber G J, Kerkhoven R M, Roberts C, Linsley P S, Bernards R, Friend S H. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002; 415 530-536
- 74 Bernard L, Babajko S, Binoux M, Ricort J M. The amino-terminal region of insulin-like growth factor binding protein-3, (1 - 95)IGFBP-3, induces apoptosis of MCF-7 breast carcinoma cells. Biochem Biophys Res Commun. 2002; 293 55-60
- 75 Butt A J, Dickson K A, McDougall F, Baxter R C. Insulin-like growth factor-binding protein-5 inhibits the growth of human breast cancer cells in vitro and in vivo. J Biol Chem. 2003; 278 29 676-29 685
- 76 Zhang X, Yee D. Insulin-like growth factor binding protein-1 (IGFBP-1) Inhibits Breast Cancer Cell Motility. Cancer Res. 2002; 62 4369-4375
- 77 Gray S G, Teh B T. Histone acetylation/deacetylation and cancer: an ”open” and ”shut” case?. Curr Mol Med. 2001; 1 401-429
- 78 Johnstone R W. Histone-deacetylase inhibitors: novel drugs for the treatment of cancer. Nat Rev Drug Discov. 2002; 1 287-299
- 79 Butt A J, Fraley K A, Firth S M, Baxter R C. IGF-binding protein-3-induced growth inhibition and apoptosis do not require cell surface binding and nuclear translocation in human breast cancer cells. Endocrinology. 2002; 143 2693-2699
- 80 McCaig C, Perks C M, Holly J M. Intrinsic actions of IGFBP-3 and IGFBP-5 on Hs578T breast cancer epithelial cells: inhibition or accentuation of attachment and survival is dependent upon the presence of fibronectin. J Cell Sci. 2002; 115 4293-4303
- 81 Weinberg W C, Denning M F. P21Waf1 control of epithelial cell cycle and cell fate. Crit Rev Oral Biol Med. 2002; 13 453-464
- 82 Dupont J, Karas M, LeRoith D. The cyclin-dependent kinase inhibitor p21CIP/WAF is a positive regulator of insulin-like growth factor I-induced cell proliferation in MCF-7 human breast cancer cells. J Biol Chem. 2003; 278 37256-37264
- 83 Opalinska J B, Gewirtz A M. Nucleic-acid therapeutics: Basic principles and recent applications. Nat Rev Drug Discov. 2002; 1 503-514
- 84 Porumb H, Gousset H, Letellier R, Salle V, Briane D, Vassy J, Amor-Gueret M, Israel L, Taillandier E. Temporary ex vivo inhibition of the expression of the human oncogene HER2 (NEU) by a triple helix-forming oligonucleotide. Cancer Res. 1996; 56 515-522
- 85 Camirand A, Lu Y, Pollak M. Co-targeting HER2/ErbB2 and insulin-like growth factor-1 receptors causes synergistic inhibition of growth in HER2-overexpressing breast cancer cells. Med Sci Monit. 2002; 8 BR521-BR526
- 86 Brodt P, Samani A, Navab R. Inhibition of the type I insulin-like growth factor receptor expression and signaling: Novel strategies for antimetastatic therapy. Biochem Pharmacol. 2000; 60 1101-1107
- 87 Chernicky C L, Tan H, Yi L, Loret de Mola J R, Ilan J. 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. 2002; 55 102-109
- 88 Jackson J G, Zhang X, Yoneda T, Yee D. Regulation of breast cancer cell motility by insulin receptor substrate- 2 (IRS-2) in metastatic variants of human breast cancer cell lines. Oncogene. 2001; 20 7318-7325
- 89 Caplen N J. RNAi as a gene therapy approach. Expert Opin Biol Ther. 2003; 3 575-586
- 90 Sohail M, Doran G, Riedemann J, Macaulay V, Southern E M. A simple and cost-effective method for producing small interfering RNAs with high efficacy. Nucl Acids Res. 2003; 31 e38
- 91 Bohula E A, Salisbury A J, Sohail M, Playford M P, Riedemann J, Southern E M, Macaulay V M. The efficacy of small interfering RNAs targeted to the type 1 insulin-like growth factor receptor (IGF1R) is influenced by secondary structure in the IGF1R transcript. J Biol Chem. 2003; 278 15991-15997
- 92 Maloney E K, McLaughlin J L, Dagdigian N E, Garrett L M, Connors K M, Zhou X M, Blattler W A, Chittenden T, Singh R. An anti-insulin-like growth factor I receptor antibody that is a potent inhibitor of cancer cell proliferation. Cancer Res. 2003; 63 5073-5083
- 93 Sachdev D, Li S L, Hartell J S, Fujita-Yamaguchi Y, Miller J S, Yee D. A chimeric humanized single-chain antibody against the type I insulin-like growth factor (IGF) receptor renders breast cancer cells refractory to the mitogenic effects of IGF-I. Cancer Res. 2003; 63 627-635
- 94 Reiss K, D'Ambrosio C, Tu X, Tu C, Baserga R. Inhibition of tumor growth by a dominant negative mutant of the insulin-like growth factor I receptor with a bystander effect. Clin Cancer Res. 1998; 4 2647-2655
- 95 Pietrzkowski Z, Wernicke D, Porcu P, Jameson B A, Baserga R. Inhibition of cellular proliferation by peptide analogues of insulin-like growth factor 1. Cancer Res. 1992; 52 6447-6451
- 96 Reiss K, Yumet G, Shan S, Huang Z, Alnemri E, Srinivasula S M, Wang J Y, Morrione A, Baserga R. Synthetic peptide sequence from the C-terminus of the insulin-like growth factor-I receptor that induces apoptosis and inhibition of tumor growth. J Cell Physiol. 1999; 181 124-135
- 97 Blume A J, Beasley J, Goldstein N I. The use of peptides in diogenesis: a novel approach to drug discovery and phenomics. Biopolymers. 2000; 55 347-356
- 98 Hofmann F, Garcia-Echeverria C, Brüggen J, Capraro H G, Cozens R, Evans D B, Fabbro D, Ferrari S, Furet P, Geiger T, Graus Porta D, Liebetanz J, Maira M S, Marti A, Martiny-Baron G, Mestan J, Meyer T, Ruetz S, Stolz B, Zimmermann J, Pearson M A. In vitro and in vivo profiling of selective and potent IGF-IR kinase inhibitors. AACR Annual Meeting. 2003; Abstract
- 99 Blum G, Gazit A, Levitzki A. Development of new insulin-like growth factor-1 receptor kinase inhibitors using catechol mimics. J Biol Chem. 2003; 278 40 442-40 454
- 100 Hubbard S R, Till J H. Protein tyrosine kinase structure and function. Annu Rev Biochem. 2000; 69 373-398
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