title: c-Myc is required for transformation of FDC-P1 cells by EGFRvIII.
abstract: In contrast to wtEGFR, its truncated version EGFRvIII transformed non-tumorigenic FDC-P1 cells only when c-Myc was coexpressed. In nude mice, EGFRvIII/c-Myc coexpressing cells induced tumors, whereas wtEGFR-expressing EGF-dependent FDC-P1 cells did not. EGFRvIII function was required for both the induction and maintenance of tumor growth. Cellular proliferation was inhibited by a selective EGFR tyrosine kinase inhibitor indicating intrinsic tyrosine kinase activities for both receptors. Unlike wtEGFR, constitutive signaling by EGFRvIII was refractory to stimulation by the EGFR ligands EGF and TGF-alpha. Summarized, EGFRvIII is a constitutively active receptor tyrosine kinase whose transforming capacity is lower than that of EGF-stimulated wtEGFR.
authors.affiliation: Department of NCE Lead Discovery, Boehringer Ingelheim Austria GmbH, Dr. Boehringer-Gasse 5-11, A-1121 Vienna, Austria.
authors.forename: Oliver
authors.initials: O
authors.lastname: Rath
authors.forename: Adi
authors.initials: A
authors.lastname: Himmler
authors.forename: Anke
authors.initials: A
authors.lastname: Baum
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sommergruber
authors.forename: Hartmut
authors.initials: H
authors.lastname: Beug
authors.forename: Thomas
authors.initials: T
authors.lastname: Metz
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D066246:ErbB Receptors / Q000235:genetics* / Q000502:physiology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D007377:Interleukin-3; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases