Ribozyme-Mediated Inhibition of 801-bp Deletion-Mutant Epidermal Growth Factor Receptor mRNA Expression in Glioblastoma Multiforme 英文参考文献.docVIP

Molecules 2010, 15, 4670-4678; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Review Ribozyme-Mediated Inhibition of 801-bp Deletion-Mutant Epidermal Growth Factor Receptor mRNA Expression in Glioblastoma Multiforme Georg Karpel-Massler, Christian Rainer Wirtz and Marc-Eric Halatsch * Department of Neurosurgery, University of Ulm Medical School, Steinh?velstr 9, D-89075 Ulm, Germany; E-Mails: georg.karpel@uniklinik-ulm.de (G.K.-M.); rainer.wirtz@uniklinik-ulm.de (C.R.W.) * Author to whom correspondence should be addressed; E-Mail: marc-eric.halatsch@uniklinik-ulm.de; Tel: +49(0)731/500-55003; Fax:+49(0)731/500-55002. Received: 8 June 2010; in revised form: 28 June 2010 / Accepted: 29 June 2010 / Published: 30 June 2010 Abstract: The epidermal growth factor receptor (HER1/EGFR) is known to be disregulated in a large subgroup of glioblastoma multiforme cases. Disregulation of HER1/EGFR is related to malignant transformation and tumor growth in various human cancers, including malignant glioma. One mechanism that may lead to disregulated HER1/EGFR signaling is the intrinsic alteration of the receptor structure due to mutational changes. The most common mutant form of HER1/EGFR, named variant III (EGFRvIII), results from an 801 bp in-frame deletion in the DNA sequence encoding the extracellular ligand-binding domain. Independent of ligand–binding, EGFRvIII is constitutively activated and beyond external control. Since its cellular expression was shown to relate enhanced tumorigenicity, various therapeutic strategies were developed to target EGFRvIII, including monoclonal antibodies, vaccination therapies and small-molecule tyrosine kinase inhibitors. In this review, we focus on ribozyme-mediated inhibition of EGFRvIII messenger RNA expression as a gene therapeutic approach for EGFRvIII-