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Advances in Brief |
Departments of Pathology [A. L., C. A. G., H. M. M., J. H. S, G. J. R.] and Surgery [H. S. F., G. E. A., J. H. S.], Duke University Medical Center, Durham, North Carolina 27710
The gene most commonly altered in human glioblastomas is the epidermalgrowth factor receptor (EGFR). We profiled transcripts induced by mutantEGFR to better understand its role in tumor progression. The pattern found suggested enhanced tumor invasion. The highly induced genes included extracellular matrix components, metalloproteases, and a serine protease. We confirmed that mutant EGFR did make glioblastoma cells both more motile and invasive using in vitro assays. Furthermore, inhibitors of EGFR (OSI-774 and Tyrphostin AG1478) selectively down-regulated these molecular effectors in glioblastoma cells, eliminating enhanced invasion.
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L. Li, A. Dutra, E. Pak, J. E. Labrie III, R. M. Gerstein, P. P. Pandolfi, L. D. Recht, and A. H. Ross EGFRvIII expression and PTEN loss synergistically induce chromosomal instability and glial tumors Neuro-oncol, January 1, 2009; 11(1): 9 - 21. [Abstract] [Full Text] [PDF] |
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E. C. Brantley and E. N. Benveniste Signal Transducer and Activator of Transcription-3: A Molecular Hub for Signaling Pathways in Gliomas Mol. Cancer Res., May 1, 2008; 6(5): 675 - 684. [Abstract] [Full Text] [PDF] |
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M. K. Nicholas, R. V. Lukas, N. F. Jafri, L. Faoro, and R. Salgia Epidermal Growth Factor Receptor-Mediated Signal Transduction in the Development and Therapy of Gliomas Clin. Cancer Res., December 15, 2006; 12(24): 7261 - 7270. [Abstract] [Full Text] [PDF] |
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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] |
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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] |
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M. Aghi, P. Gaviani, J. W. Henson, T. T. Batchelor, D. N. Louis, and F. G. Barker II Magnetic Resonance Imaging Characteristics Predict Epidermal Growth Factor Receptor Amplification Status in Glioblastoma Clin. Cancer Res., December 15, 2005; 11(24): 8600 - 8605. [Abstract] [Full Text] [PDF] |
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I. C. Cuevas, A. L. Slocum, P. Jun, J. F. Costello, A. W. Bollen, G. J. Riggins, M. W. McDermott, and A. Lal Meningioma Transcript Profiles Reveal Deregulated Notch Signaling Pathway Cancer Res., June 15, 2005; 65(12): 5070 - 5075. [Abstract] [Full Text] [PDF] |
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Y. Zhang, Y.-f. Zhang, J. Bryant, A. Charles, R. J. Boado, and W. M. Pardridge Intravenous RNA Interference Gene Therapy Targeting the Human Epidermal Growth Factor Receptor Prolongs Survival in Intracranial Brain Cancer Clin. Cancer Res., June 1, 2004; 10(11): 3667 - 3677. [Abstract] [Full Text] [PDF] |
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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] |
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R. Perez-Soler HER1/EGFR Targeting: Refining the Strategy Oncologist, February 1, 2004; 9(1): 58 - 67. [Abstract] [Full Text] [PDF] |
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M. L. Janmaat and G. Giaccone Small-Molecule Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Oncologist, December 1, 2003; 8(6): 576 - 586. [Abstract] [Full Text] [PDF] |
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B. Hu, P. Guo, Q. Fang, H.-Q. Tao, D. Wang, M. Nagane, H.-J. Su Huang, Y. Gunji, R. Nishikawa, K. Alitalo, et al. Angiopoietin-2 induces human glioma invasion through the activation of matrix metalloprotease-2 PNAS, July 22, 2003; 100(15): 8904 - 8909. [Abstract] [Full Text] [PDF] |
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J. Mendelsohn and J. Baselga Status of Epidermal Growth Factor Receptor Antagonists in the Biology and Treatment of Cancer J. Clin. Oncol., July 15, 2003; 21(14): 2787 - 2799. [Abstract] [Full Text] [PDF] |
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M. Matsuo, H. Sakurai, and I. Saiki ZD1839, a Selective Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Shows Antimetastatic Activity Using a Hepatocellular Carcinoma Model Mol. Cancer Ther., June 1, 2003; 2(6): 557 - 561. [Abstract] [Full Text] [PDF] |
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M. H. H. Schmidt, F. B. Furnari, W. K. Cavenee, and O. Bogler Epidermal growth factor receptor signaling intensity determines intracellular protein interactions, ubiquitination, and internalization PNAS, May 27, 2003; 100(11): 6505 - 6510. [Abstract] [Full Text] [PDF] |
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Y. Okada, E. E. Hurwitz, J. M. Esposito, M. A. Brower, C. L. Nutt, and D. N. Louis Selection Pressures of TP53 Mutation and Microenvironmental Location Influence Epidermal Growth Factor Receptor Gene Amplification in Human Glioblastomas Cancer Res., January 15, 2003; 63(2): 413 - 416. [Abstract] [Full Text] [PDF] |
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