Role for the epidermal growth factor receptor in neurofibromatosis-related peripheral nerve tumorigenesis

Benjamin C. Ling; Jianqiang Wu; Shyra J. Miller; Kelly R. Monk; Rania Shamekh; Tilat A. Rizvi; Gabrielle Decourten-Myers; Kristine S. Vogel; Jeffrey E. Declue; Nancy Ratner

doi:10.1016/j.ccr.2004.10.016

Role for the epidermal growth factor receptor in neurofibromatosis-related peripheral nerve tumorigenesis

Benjamin C. Ling, Jianqiang Wu, Shyra J. Miller, Kelly R. Monk, Rania Shamekh, Tilat A. Rizvi, Gabrielle Decourten-Myers, Kristine S. Vogel, Jeffrey E. Declue, Nancy Ratner

Research output: Contribution to journal › Article › peer-review

115 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	65-75
Number of pages	11
Journal	Cancer Cell
Volume	7
Issue number	1
DOIs	https://doi.org/10.1016/j.ccr.2004.10.016
State	Published - Jan 2005
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccr.2004.10.016

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title = "Role for the epidermal growth factor receptor in neurofibromatosis-related peripheral nerve tumorigenesis",

abstract = "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.",

author = "Ling, {Benjamin C.} and Jianqiang Wu and Miller, {Shyra J.} and Monk, {Kelly R.} and Rania Shamekh and Rizvi, {Tilat A.} and Gabrielle Decourten-Myers and Vogel, {Kristine S.} and Declue, {Jeffrey E.} and Nancy Ratner",

note = "Funding Information: We thank Doug Lowy (NCI) for reviewing the manuscript, Charles Kuntz (University of Cincinnati) for helpful discussion, Frank Sharp (University of Cincinnati) for use of the ABI7700 Sequence Detector, Brian Weiss for assistance with statistics, and the University of Cincinnati Transgenic Core for generation of CNPase-hEGFR mice. We thank Maureen Fitzgerald for electron microscopy. This work was supported by grants NIH NS28840 and the DAMD-17-02-1-0679 to N.R. J.W. is a DAMD Neurofibromatosis Fellow. B.C.L. was supported by a fellowship from the Ohio ACS. A NMSS Advanced postdoctoral fellowship and the DOD support S.J.M. K.R.M. was supported by T32-CA-59268 and the Albert J. Ryan Foundation.",

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AU - Ling, Benjamin C.

AU - Wu, Jianqiang

AU - Miller, Shyra J.

AU - Monk, Kelly R.

AU - Shamekh, Rania

AU - Rizvi, Tilat A.

AU - Decourten-Myers, Gabrielle

AU - Vogel, Kristine S.

AU - Declue, Jeffrey E.

AU - Ratner, Nancy

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N2 - 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.

AB - 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.

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Role for the epidermal growth factor receptor in neurofibromatosis-related peripheral nerve tumorigenesis

Abstract

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