Role for the epidermal growth factor receptor in neurofibromatosis-related peripheral nerve tumorigenesis.
Benign neurofibromas and malignant peripheral nerve sheath tumors are serious complications of neurofibromatosis type 1. The epidermal growth factor receptor is not expressed by normal Schwann cells, yet is overexpressed in subpopulations of Nf1 mutant Schwann cells. We evaluated the role of EGFR in Schwann cell tumorigenesis. Expression of EGFR in transgenic mouse Schwann cells elicited features of neurofibromas: Schwann cell hyperplasia, excess collagen, mast cell accumulation, and progressive dissociation of non-myelin-forming Schwann cells from axons. Mating EGFR transgenic mice to Nf1 hemizygotes did not enhance this phenotype. Genetic reduction of EGFR in Nf1(+/-);p53(+/-) mice that develop sarcomas significantly improved survival. Thus, gain- and loss-of-function experiments support the relevance of EGFR to peripheral nerve tumor formation.
Ling
Benjamin C
BC
Departments of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Wu
Jianqiang
J
Miller
Shyra J
SJ
Monk
Kelly R
KR
Shamekh
Rania
R
Rizvi
Tilat A
TA
Decourten-Myers
Gabrielle
G
Vogel
Kristine S
KS
DeClue
Jeffrey E
JE
Ratner
Nancy
N
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009380:Neoplasms, Nerve Tissue / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009455:Neurofibroma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009456:Neurofibromatosis 1 / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D025542:Neurofibromin 1 / Q000235:genetics / Q000378:metabolism; D010525:Peripheral Nerves / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D025542:Neurofibromin 1; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases