In situ analysis of mutant EGFRs prevalent in glioblastoma multiforme reveals aberrant dimerization, activation, and differential response to anti-EGFR targeted therapy

Molecular Cancer Research

Volumn 10, Issue 3, 2012, Pages 428-440

  Gajadhar, Aaron S ^a   Bogdanovic, Elena ^a   Muñoz, Diana Marcela ^a   Guha, Abhijit ^a,b  

^a HOSPITAL FOR SICK CHILDREN   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CETUXIMAB; EGFRC958 PROTEIN; EGFRVIII PROTEIN; EPIDERMAL GROWTH FACTOR RECEPTOR; MATUZUMAB; MUTANT PROTEIN; PANITUMUMAB; UNCLASSIFIED DRUG;

ABERRANT DIMERIZATION; ANIMAL CELL; ANIMAL CELL CULTURE; ARTICLE; CHO CELL; DIMERIZATION; FEMALE; FLOW CYTOMETRY; GENETIC TRANSFECTION; GLIOBLASTOMA; IMAGE ANALYSIS; IMMUNOBLOTTING; IN SITU HYBRIDIZATION; MOLECULARLY TARGETED THERAPY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; QUANTITATIVE ANALYSIS; SIGNAL NOISE RATIO;

ANIMALS; ANTIBODIES, NEOPLASM; BIOLOGICAL ASSAY; CHO CELLS; CRICETINAE; CRICETULUS; ENZYME ACTIVATION; EPITOPES; GLIOBLASTOMA; HUMANS; IMMUNOBLOTTING; MOLECULAR TARGETED THERAPY; MUTANT PROTEINS; PHOSPHORYLATION; PROTEIN MULTIMERIZATION; RECEPTOR, EPIDERMAL GROWTH FACTOR; SIGNAL-TO-NOISE RATIO;

EID: 84858591526     PISSN: 15417786     EISSN: 15573125     Source Type: Journal    
DOI: 10.1158/1541-7786.MCR-11-0531     Document Type: Article

References (32)

1. Ekstrand AJ, Sugawa N, James CD, Collins VP. Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. Proc Natl Acad Sci U S A 1992;89:4309-13.
2. Libermann TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H, et al. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 1985;313:144-7. (Pubitemid 15192341)
3. Sugawa N, Ekstrand AJ, James CD, Collins VP. Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc Natl Acad Sci U S A 1990;87:8602-6.
4. Aldape KD, Ballman K, Furth A, Buckner JC, Giannini C, Burger PC, et al. Immunohistochemical detection of EGFRvIII in high malignancy grade astrocytomas and evaluation of prognostic significance. J Neuropathol Exp Neurol 2004;63:700-7. (Pubitemid 38891086)
5. Zandi R, Larsen AB, Andersen P, Stockhausen MT, Poulsen HS. Mechanisms for oncogenic activation of the epidermal growth factor receptor. Cell Signal 2007;19:2013-23. (Pubitemid 47353811)
6. Eley G, Frederick L, Wang XY, Smith DI, James CD. 30 end structure and rearrangements of EGFR in glioblastomas. Genes Chromosomes Cancer 1998;23:248-54. (Pubitemid 28465642)
7. Frederick L, Wang XY, Eley G, James CD. Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer Res 2000;60:1383-7. (Pubitemid 30152011)
8. Pillay V, Allaf L, Wilding AL, Donoghue JF, Court NW, Greenall SA, et al. The plasticity of oncogene addiction: implications for targeted therapies directed to receptor tyrosine kinases. Neoplasia 2009;11:448-58, 2 p following 458.
9. Luwor RB, Zhu HJ, Walker F, Vitali AA, Perera RM, Burgess AW, et al. The tumor-specific de2-7 epidermal growth factor receptor (EGFR) promotes cells survival and heterodimerizes with the wild-type EGFR. Oncogene 2004;23:6095-104. (Pubitemid 39178862)
10. Gajadhar A, Guha A. A proximity ligation assay using transiently transfected, epitope-tagged proteins: application for in situ detection of dimerized receptor tyrosine kinases. Biotechniques 2010;48: 145-52.
11. Jarvius M, Paulsson J, Weibrecht I, Leuchowius KJ, Andersson AC, Wahlby C, et al. In situ detection of phosphorylated platelet-derived growth factor receptor beta using a generalized proximity ligation method. Mol Cell Proteomics 2007;6:1500-9. (Pubitemid 47506163)
12. Chu CT, Everiss KD, Wikstrand CJ, Batra SK, Kung HJ, Bigner DD. Receptor dimerization is not a factor in the signalling activity of a transforming variant epidermal growth factor receptor (EGFRvIII). Biochem J 1997;324:855-61. (Pubitemid 27285544)
13. Fernandes H, Cohen S, Bishayee S. Glycosylation-induced conformational modification positively regulates receptor-receptor association: a study with an aberrant epidermal growth factor receptor (EGFRvIII/DeltaEGFR) expressed in cancer cells. J Biol Chem 2001; 276:5375-83.
14. Huang HS, Nagane M, Klingbeil CK, Lin H, NishikawaR, Ji XD, et al. The enhanced tumorigenic activity of a mutant epidermal growth factor receptor common in human cancers is mediated by threshold levels of constitutive tyrosine phosphorylation and unattenuated signaling. J Biol Chem 1997;272:2927-35. (Pubitemid 27053343)
15. Pines G, Huang PH, Zwang Y, White FM, Yarden Y. EGFRvIV: a previously uncharacterized oncogenic mutant reveals a kinase autoinhibitory mechanism. Oncogene 2010;29:5850-60.
16. Wikstrand CJ, McLendon RE, Friedman AH, Bigner DD. Cell surface localization and density of the tumor-associated variant of the epidermal growth factor receptor, EGFRvIII. Cancer Res 1997;57:4130-40. (Pubitemid 27427708)
17. Chung I, Akita R, Vandlen R, Toomre D, Schlessinger J, Mellman I. Spatial control of EGF receptor activation by reversible dimerization on living cells. Nature 2010;464:783-7.
18. Moriki T, Maruyama H, Maruyama IN. Activation of preformed EGF receptor dimers by ligand-induced rotation of the transmembrane domain. J Mol Biol 2001;311:1011-26. (Pubitemid 32803717)
19. Sako Y, Minoghchi S, Yanagida T. Single-molecule imaging of EGFR signalling on the surface of living cells. Nat Cell Biol 2000;2:168-72.
20. Yu X, Sharma KD, Takahashi T, Iwamoto R, Mekada E. Ligand-independent dimer formation of epidermal growth factor receptor (EGFR) is a step separable from ligand-induced EGFR signaling. Mol Biol Cell 2002;13:2547-57. (Pubitemid 34831354)
21. Jura N, Endres NF, Engel K, Deindl S, Das R, Lamers MH, et al. Mechanism for activation of the EGF receptor catalytic domain by the juxtamembrane segment. Cell 2009;137:1293-307.
22. Huang PH, Miraldi ER, Xu AM, Kundukulam VA, Del Rosario AM, Flynn RA, et al. Phosphotyrosine signaling analysis of site-specific mutations on EGFRvIII identifies determinants governing glioblastoma cell growth. Mol Biosyst 2010;6:1227-37.
23. Walker F, Orchard SG, Jorissen RN, Hall NE, Zhang HH, Hoyne PA, et al. CR1/CR2 interactions modulate the functions of the cell surface epidermal growth factor receptor. J Biol Chem 2004;279: 22387-98. (Pubitemid 38679436)
24. Filmus J, Pollak MN, Cairncross JG, Buick RN. Amplified, overexpressed and rearranged epidermal growth factor receptor gene in a human astrocytoma cell line. Biochem Biophys Res Commun 1985;131:207-15. (Pubitemid 16251136)
25. Sunada H, Yu P, Peacock JS, Mendelsohn J. Modulation of tyrosine, serine, and threonine phosphorylation and intracellular processing of the epidermal growth factor receptor by antireceptor monoclonal antibody. J Cell Physiol 1990;142:284-92.
26. Yang XD, Jia XC, Corvalan JR, Wang P, Davis CG. Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol 2001;38:17-23. (Pubitemid 32194591)
27. Schmiedel J, Blaukat A, Li S, Knochel T, Ferguson KM. Matuzumab binding to EGFR prevents the conformational rearrangement required for dimerization. Cancer Cell 2008;13:365-73. (Pubitemid 351446197)
28. Leahy DJ. A molecular view of anti-ErbB monoclonal antibody therapy. Cancer Cell 2008;13:291-3. (Pubitemid 351446199)
29. Boerner JL, Danielsen A, Maihle NJ. Ligand-independent oncogenic signaling by the epidermal growth factor receptor: v-ErbB as a paradigm. Exp Cell Res 2003;284:111-21. (Pubitemid 36331970)
30. Biernat W, Huang H, Yokoo H, Kleihues P, Ohgaki H. Predominant expression of mutant EGFR (EGFRvIII) is rare in primary glioblastomas. Brain Pathol 2004;14:131-6. (Pubitemid 38656384)
31. Nishikawa R, Sugiyama T, Narita Y, Furnari F, Cavenee WK, Matsutani M. Immunohistochemical analysis of the mutant epidermal growth factor, deltaEGFR, in glioblastoma. Brain Tumor Pathol 2004;21:53-6. (Pubitemid 39518146)
32. Shinojima N, Tada K, Shiraishi S, Kamiryo T, Kochi M, Nakamura H, et al. Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. Cancer Res 2003;63: 6962-70. (Pubitemid 37322983)