CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Batra, S. K.
Right arrow Articles by Bigner, D. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Batra, S. K.
Right arrow Articles by Bigner, D. D.

Cell Growth & Differentiation, Vol 6, Issue 10 1251-1259, Copyright © 1995 by American Association of Cancer Research

ARTICLES

Epidermal growth factor ligand-independent, unregulated, cell-transforming potential of a naturally occurring human mutant EGFRvIII gene

SK Batra, S Castelino-Prabhu, CJ Wikstrand, X Zhu, PA Humphrey, HS Friedman and DD Bigner
Duke University Medical Center, Durham, North Carolina 27710, USA.

The type III deletion-mutant gene for the epidermal growth factor receptor (EGFRvIII) is frequently expressed in glioblastomas and in breast and non-small cell lung carcinomas. To understand its contribution to the malignant phenotype in humans, we transfected NR6 cells with the mammalian vector pH beta APr-1-neo containing cDNA for either EGFRvIII or wild-type EGFR. Western blot analyses showed that NR6 transfected with wild-type EGFR (NR6W) contained a normal-sized protein (170 kilodaltons); cells transfected with EGFRvIII (NR6M) contained a truncated protein (145 kilodaltons). NR6W cells demonstrated a saturation binding curve with 125I-labeled EGF (affinity, 1.8 x 10(8); r2 = 0.96). NR6M cells, however, showed a low but consistent level of 125I-labeled EGF binding (affinity, 4 x 10(7); r2 = 0.99) compared with NR6, which lacked binding. The population doubling time was shorter for NR6M (0.64 days) than for NR6W (1.1 days) and NR6V (2.27 days). Soft agar focus formation assay by NR6M was 4- to 5-fold higher than that by NR6W. In nude mice, NR6M (1 x 10(7) cells), without exogenous ligand, formed tumors within 12 days; no tumors were observed over 90 days in mice receiving identical doses of NR6W, NR6V, or NR6 cells. EGF stimulated autophosphorylation of receptor in NR6W (4- to 9-fold) but caused only slight (1.8- to 1.9-fold) to no enhancement in NR6M. Further, there was no difference in constitutive tyrosine kinase activity between NR6M and NR6W. Our results clearly indicate that EGFRvIII functions as an oncoprotein, but its intrinsic tyrosine kinase activity may not be responsible for its biological function.


This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
D. A. Reardon, A. Desjardins, J. J. Vredenburgh, D. M. O'Rourke, D. D. Tran, K. L. Fink, L. B. Nabors, G. Li, D. A. Bota, R. V. Lukas, et al.
Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial
Clin. Cancer Res., April 1, 2020; 26(7): 1586 - 1594.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
A. Roos, H. D. Dhruv, S. Peng, L. J. Inge, S. Tuncali, M. Pineda, N. Millard, Z. Mayo, J. M. Eschbacher, J. C. Loftus, et al.
EGFRvIII-Stat5 Signaling Enhances Glioblastoma Cell Migration and Survival
Mol. Cancer Res., July 1, 2018; 16(7): 1185 - 1195.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. L. Hein, P. Seshacharyulu, S. Rachagani, Y. M. Sheinin, M. M. Ouellette, M. P. Ponnusamy, M. C. Mumby, S. K. Batra, and Y. Yan
PR55{alpha} Subunit of Protein Phosphatase 2A Supports the Tumorigenic and Metastatic Potential of Pancreatic Cancer Cells by Sustaining Hyperactive Oncogenic Signaling
Cancer Res., April 15, 2016; 76(8): 2243 - 2253.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
V. C. Saunders, M. Lafitte, I. Adrados, V. Quereda, D. Feurstein, Y. Ling, M. Fallahi, L. H. Rosenberg, and D. R. Duckett
Identification of an EGFRvIII-JNK2-HGF/c-Met-Signaling Axis Required for Intercellular Crosstalk and Glioblastoma Multiforme Cell Invasion
Mol. Pharmacol., December 1, 2015; 88(6): 962 - 969.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
E. B. Reilly, A. C. Phillips, F. G. Buchanan, G. Kingsbury, Y. Zhang, J. A. Meulbroek, T. B. Cole, P. J. DeVries, H. D. Falls, C. Beam, et al.
Characterization of ABT-806, a Humanized Tumor-Specific Anti-EGFR Monoclonal Antibody
Mol. Cancer Ther., May 1, 2015; 14(5): 1141 - 1151.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
V. Chandramohan, X. Bao, S. T. Keir, C. N. Pegram, S. E. Szafranski, H. Piao, C. J. Wikstrand, R. E. McLendon, C.-T. Kuan, I. H. Pastan, et al.
Construction of an Immunotoxin, D2C7-(scdsFv)-PE38KDEL, Targeting EGFRwt and EGFRvIII for Brain Tumor Therapy
Clin. Cancer Res., September 1, 2013; 19(17): 4717 - 4727.
[Abstract] [Full Text] [PDF]

Home page
 MCPHome page
H. Johnson, A. M. Del Rosario, B. D. Bryson, M. A. Schroeder, J. N. Sarkaria, and F. M. White
Molecular Characterization of EGFR and EGFRvIII Signaling Networks in Human Glioblastoma Tumor Xenografts
Mol. Cell. Proteomics, December 1, 2012; 11(12): 1724 - 1740.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. E. Wheeler, E. M. Morariu, J. S. Bednash, C. G. Otte, R. R. Seethala, S. I. Chiosea, and J. R. Grandis
Lyn Kinase Mediates Cell Motility and Tumor Growth in EGFRvIII-Expressing Head and Neck Cancer
Clin. Cancer Res., May 15, 2012; 18(10): 2850 - 2860.
[Abstract] [Full Text] [PDF]

Home page
 Cancer DiscoveryHome page
I. Vivanco, H. I. Robins, D. Rohle, C. Campos, C. Grommes, P. L. Nghiemphu, S. Kubek, B. Oldrini, M. G. Chheda, N. Yannuzzi, et al.
Differential Sensitivity of Glioma- versus Lung Cancer-Specific EGFR Mutations to EGFR Kinase Inhibitors
Cancer Discovery, May 1, 2012; 2(5): 458 - 471.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. Mascaux, M. W. Wynes, Y. Kato, C. Tran, B. R. Asuncion, J. M. Zhao, M. Gustavson, J. Ranger-Moore, F. Gaire, J. Matsubayashi, et al.
EGFR Protein Expression in Non-Small Cell Lung Cancer Predicts Response to an EGFR Tyrosine Kinase Inhibitor--A Novel Antibody for Immunohistochemistry or AQUA Technology
Clin. Cancer Res., December 15, 2011; 17(24): 7796 - 7807.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Genomics ProteomicsHome page
U. H. Weidle, D. Maisel, S. Klostermann, E. H. Weiss, and M. Schmitt
Differential Splicing Generates New Transmembrane Receptor and Extracellular Matrix-related Targets for Antibody-based Therapy of Cancer
Cancer Genomics Proteomics, September 1, 2011; 8(5): 211 - 226.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. H. Sampson, A. B. Heimberger, G. E. Archer, K. D. Aldape, A. H. Friedman, H. S. Friedman, M. R. Gilbert, J. E. Herndon II, R. E. McLendon, D. A. Mitchell, et al.
Immunologic Escape After Prolonged Progression-Free Survival With Epidermal Growth Factor Receptor Variant III Peptide Vaccination in Patients With Newly Diagnosed Glioblastoma
J. Clin. Oncol., November 1, 2010; 28(31): 4722 - 4729.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
J. H. Sampson, G. E. Archer, D. A. Mitchell, A. B. Heimberger, J. E. Herndon II, D. Lally-Goss, S. McGehee-Norman, A. Paolino, D. A. Reardon, A. H. Friedman, et al.
An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme
Mol. Cancer Ther., October 1, 2009; 8(10): 2773 - 2779.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
G. Karpel-Massler, U. Schmidt, A. Unterberg, and M.-E. Halatsch
Therapeutic Inhibition of the Epidermal Growth Factor Receptor in High-Grade Gliomas: Where Do We Stand?
Mol. Cancer Res., July 1, 2009; 7(7): 1000 - 1012.
[Abstract] [Full Text] [PDF]

Home page
 J Biol ChemHome page
T. Okamura, S. Singh, J. Buolamwini, T. Haystead, H. Friedman, D. Bigner, and F. Ali-Osman
Tyrosine Phosphorylation of the Human Glutathione S-Transferase P1 by Epidermal Growth Factor Receptor
J. Biol. Chem., June 19, 2009; 284(25): 16979 - 16989.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
F. G. Pernas, C. T. Allen, M. E. Winters, B. Yan, J. Friedman, B. Dabir, K. Saigal, G. S. Mundinger, X. Xu, J. C. Morris, et al.
Proteomic Signatures of Epidermal Growth Factor Receptor and Survival Signal Pathways Correspond to Gefitinib Sensitivity in Head and Neck Cancer
Clin. Cancer Res., April 1, 2009; 15(7): 2361 - 2372.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
J. E. Duex and A. Sorkin
RNA Interference Screen Identifies Usp18 as a Regulator of Epidermal Growth Factor Receptor Synthesis
Mol. Biol. Cell, March 15, 2009; 20(6): 1833 - 1844.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. A. Fromm, S. A. S. Johnson, and D. L. Johnson
Epidermal Growth Factor Receptor 1 (EGFR1) and Its Variant EGFRvIII Regulate TATA-Binding Protein Expression through Distinct Pathways
Mol. Cell. Biol., October 15, 2008; 28(20): 6483 - 6495.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
E. Arwert, S. Hingtgen, J.-L. Figueiredo, H. Bergquist, U. Mahmood, R. Weissleder, and K. Shah
Visualizing the Dynamics of EGFR Activity and Antiglioma Therapies In vivo
Cancer Res., August 1, 2007; 67(15): 7335 - 7342.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. B. Gendreau, R. Ventura, P. Keast, A. D. Laird, F. M. Yakes, W. Zhang, F. Bentzien, B. Cancilla, J. Lutman, F. Chu, et al.
Inhibition of the T790M Gatekeeper Mutant of the Epidermal Growth Factor Receptor by EXEL-7647
Clin. Cancer Res., June 15, 2007; 13(12): 3713 - 3723.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. C. Sok, F. M. Coppelli, S. M. Thomas, M. N. Lango, S. Xi, J. L. Hunt, M. L. Freilino, M. W. Graner, C. J. Wikstrand, D. D. Bigner, et al.
Mutant Epidermal Growth Factor Receptor (EGFRvIII) Contributes to Head and Neck Cancer Growth and Resistance to EGFR Targeting
Clin. Cancer Res., September 1, 2006; 12(17): 5064 - 5073.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. N. Blehm, P. E. Spiess, J. E. Bondaruk, M. E. Dujka, G. J. Villares, Y.-j. Zhao, O. Bogler, K. D. Aldape, H. B. Grossman, L. Adam, et al.
Mutations Within the Kinase Domain and Truncations of the Epidermal Growth Factor Receptor Are Rare Events in Bladder Cancer: Implications for Therapy
Clin. Cancer Res., August 1, 2006; 12(15): 4671 - 4677.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. B. Ramnarain, S. Park, D. Y. Lee, K. J. Hatanpaa, S. O. Scoggin, H. Otu, T. A. Libermann, J. M. Raisanen, R. Ashfaq, E. T. Wong, et al.
Differential Gene Expression Analysis Reveals Generation of an Autocrine Loop by a Mutant Epidermal Growth Factor Receptor in Glioma Cells
Cancer Res., January 15, 2006; 66(2): 867 - 874.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
R. K. Goudar, Q. Shi, M. D. Hjelmeland, S. T. Keir, R. E. McLendon, C. J. Wikstrand, E. D. Reese, C. A. Conrad, P. Traxler, H. A. Lane, et al.
Combination therapy of inhibitors of epidermal growth factor receptor/vascular endothelial growth factor receptor 2 (AEE788) and the mammalian target of rapamycin (RAD001) offers improved glioblastoma tumor growth inhibition
Mol. Cancer Ther., January 1, 2005; 4(1): 101 - 112.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
W. Yang, R. F. Barth, G. Wu, M. J. Ciesielski, R. A. Fenstermaker, B. A. Moffat, B. D. Ross, and C. J. Wikstrand
Development of a Syngeneic Rat Brain Tumor Model Expressing EGFRvIII and Its Use for Molecular Targeting Studies with Monoclonal Antibody L8A4
Clin. Cancer Res., January 1, 2005; 11(1): 341 - 350.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Zhan and D. M. O'Rourke
SHP-2-Dependent Mitogen-Activated Protein Kinase Activation Regulates EGFRvIII but not Wild-Type Epidermal Growth Factor Receptor Phosphorylation and Glioblastoma Cell Survival
Cancer Res., November 15, 2004; 64(22): 8292 - 8298.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
E. Purev, D. Cai, E. Miller, R. Swoboda, T. Mayer, A. Klein-Szanto, F. M. Marincola, R. Mick, L. Otvos, W. Wunner, et al.
Immune Responses of Breast Cancer Patients to Mutated Epidermal Growth Factor Receptor (EGF-RvIII, {Delta}EGF-R, and de2-7 EGF-R)
J. Immunol., November 15, 2004; 173(10): 6472 - 6480.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. Lammering, T. H. Hewit, M. Holmes, K. Valerie, W. Hawkins, P.-S. Lin, R. B. Mikkelsen, and R. K. Schmidt-Ullrich
Inhibition of the Type III Epidermal Growth Factor Receptor Variant Mutant Receptor by Dominant-Negative EGFR-CD533 Enhances Malignant Glioma Cell Radiosensitivity
Clin. Cancer Res., October 1, 2004; 10(19): 6732 - 6743.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. A. Learn, T. L. Hartzell, C. J. Wikstrand, G. E. Archer, J. N. Rich, A. H. Friedman, H. S. Friedman, D. D. Bigner, and J. H. Sampson
Resistance to Tyrosine Kinase Inhibition by Mutant Epidermal Growth Factor Receptor Variant III Contributes to the Neoplastic Phenotype of Glioblastoma Multiforme
Clin. Cancer Res., May 1, 2004; 10(9): 3216 - 3224.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. N. Rich, D. A. Reardon, T. Peery, J. M. Dowell, J. A. Quinn, K. L. Penne, C. J. Wikstrand, L. B. Van Duyn, J. E. Dancey, R. E. McLendon, et al.
Phase II Trial of Gefitinib in Recurrent Glioblastoma
J. Clin. Oncol., January 1, 2004; 22(1): 133 - 142.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. B. Heimberger, L. E. Crotty, G. E. Archer, K. R. Hess, C. J. Wikstrand, A. H. Friedman, H. S. Friedman, D. D. Bigner, and J. H. Sampson
Epidermal Growth Factor Receptor VIII Peptide Vaccination Is Efficacious against Established Intracerebral Tumors
Clin. Cancer Res., September 15, 2003; 9(11): 4247 - 4254.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Mamot, D. C. Drummond, U. Greiser, K. Hong, D. B. Kirpotin, J. D. Marks, and J. W. Park
Epidermal Growth Factor Receptor (EGFR)-targeted Immunoliposomes Mediate Specific and Efficient Drug Delivery to EGFR- and EGFRvIII-overexpressing Tumor Cells
Cancer Res., June 15, 2003; 63(12): 3154 - 3161.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. B. Heimberger, C. A. Learn, G. E. Archer, R. E. McLendon, T. A. Chewning, F. L. Tuck, J. B. Pracyk, A. H. Friedman, H. S. Friedman, D. D. Bigner, et al.
Brain Tumors in Mice Are Susceptible to Blockade of Epidermal Growth Factor Receptor (EGFR) with the Oral, Specific, EGFR-Tyrosine Kinase Inhibitor ZD1839 (Iressa)
Clin. Cancer Res., November 1, 2002; 8(11): 3496 - 3502.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. Lammering, K. Valerie, P.-S. Lin, R. B. Mikkelsen, J. N. Contessa, J. P. Feden, J. Farnsworth, P. Dent, and R. K. Schmidt-Ullrich
Radiosensitization of Malignant Glioma Cells through Overexpression of Dominant-Negative Epidermal Growth Factor Receptor
Clin. Cancer Res., March 1, 2001; 7(3): 682 - 690.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. H. Sampson, L. E. Crotty, S. Lee, G. E. Archer, D. M. Ashley, C. J. Wikstrand, L. P. Hale, C. Small, G. Dranoff, A. H. Friedman, et al.
Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors
PNAS, June 20, 2000; 97(13): 7503 - 7508.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. K. Tang, X.-Q. Gong, D. K. Moscatello, A. J. Wong, and M. E. Lippman
Epidermal Growth Factor Receptor vIII Enhances Tumorigenicity in Human Breast Cancer
Cancer Res., June 1, 2000; 60(11): 3081 - 3087.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. Frederick, X.-Y. Wang, G. Eley, and C. D. James
Diversity and Frequency of Epidermal Growth Factor Receptor Mutations in Human Glioblastomas
Cancer Res., March 1, 2000; 60(5): 1383 - 1387.
[Abstract] [Full Text]

Home page
 Clin. Cancer Res.Home page
M. Bredel, I. F. Pollack, R. L. Hamilton, and C. D. James
Epidermal Growth Factor Receptor Expression and Gene Amplification in High-Grade Non-Brainstem Gliomas of Childhood
Clin. Cancer Res., July 1, 1999; 5(7): 1786 - 1792.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C.-T. Kuan, C. J. Reist, C. F. Foulon, I. A. J. Lorimer, G. Archer, C. N. Pegram, I. Pastan, M. R. Zalutsky, and D. D. Bigner
125I-labeled Anti-Epidermal Growth Factor Receptor-vIII Single-Chain Fv Exhibits Specific and High-Level Targeting of Glioma Xenografts
Clin. Cancer Res., June 1, 1999; 5(6): 1539 - 1549.
[Abstract] [Full Text] [PDF]

Home page
 J Biol ChemHome page
D. K. Moscatello, M. Holgado-Madruga, D. R. Emlet, R. B. Montgomery, and A. J. Wong
Constitutive Activation of Phosphatidylinositol 3-Kinase by a Naturally Occurring Mutant Epidermal Growth Factor Receptor
J. Biol. Chem., January 2, 1998; 273(1): 200 - 206.
[Abstract] [Full Text] [PDF]

Home page
 J Biol ChemHome page
S. A. Prigent, M. Nagane, H. Lin, I. Huvar, G. R. Boss, J. R. Feramisco, W. K. Cavenee, and H.- J. S. Huang
Enhanced Tumorigenic Behavior of Glioblastoma Cells Expressing a Truncated Epidermal Growth Factor Receptor Is Mediated through the Ras-Shc-Grb2 Pathway
J. Biol. Chem., October 11, 1996; 271(41): 25639 - 25645.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. H. Sampson, L. E. Crotty, S. Lee, G. E. Archer, D. M. Ashley, C. J. Wikstrand, L. P. Hale, C. Small, G. Dranoff, A. H. Friedman, et al.
Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors
PNAS, June 20, 2000; 97(13): 7503 - 7508.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1995 by the American Association of Cancer Research.