Beckman Coulter Application (system and method support)
ProteomeLab™ PF 2D Analysis of Genetically-Characterized Human Glioma Xenografts
Victoria Ioffe1, Ashken Movsisyan1, Jiuhong Yu1, C. David James2, and Oliver Bögler1
- William and Karen Davidson Laboratory, Hermelin Brain Center, Department of Neurosurgery, Henry Ford Hospital, Detroit, MI
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
Dysregulation of receptor tyrosine kinase signaling is a major contributor to cancer, including gliomas. High level expression of epidermal growth factor receptor (EGFR) is frequently observed in glioma, usually in combination with wild-type and/or mutant EGFR gene amplification that has been associated with reduced survival. The most common of the rearrangements leads to the deletion of exons 2–7 in the EGFR mRNA, causing an in-frame deletion of 801 bp of sequence coding for a portion of the extracellular domain. The resulting protein, deleted-(2–7) EGFR (also known as EGFRvIII, EGFR* and ∆EGFR, which are referred to here as ∆EGFR), is expressed primarily in glioblastoma/astrocytoma grade IV. ∆EGFR, which can transform NIH3T3 cells, confers enhanced tumorigenicity to glioma cells in vivo, enhances cell tumorigenicity and growth rates while reducing apoptosis. ∆EGFR is phosphorylated in a ligand-independent fashion in the absence of significant internalization and down regulation. Therefore, ∆EGFR is a potent glioma oncogene and understanding its aberrant signaling is important.
We are using a novel proteomics approach, the ProteomeLab™ PF 2D from Beckman Coulter, to identify molecular differences between glioma cells bearing amplified EGFR and amplified ∆EGFR in human glioma xenografts as one approach to understanding ∆EGFR. One advantage of this approach is that alterations in the proteome due to changes in signaling pathways, such as phosphorylation levels, are more easily detected by proteomics than genomics.
* All trademarks are the property of their respective owners. Where applicable, the PCR process is covered by patents owned by Roche Molecular Systems, Inc., and F. Hoffman-LaRoche, Ltd.
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- 2006 Beckman Coulter, Inc.
