c-Myc is required for transformation of FDC-P1 cells by EGFRvIII.
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.
Rath
Oliver
O
Department of NCE Lead Discovery, Boehringer Ingelheim Austria GmbH, Dr. Boehringer-Gasse 5-11, A-1121 Vienna, Austria.
Himmler
Adi
A
Baum
Anke
A
Sommergruber
Wolfgang
W
Beug
Hartmut
H
Metz
Thomas
T
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
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