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

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

Research output: Contribution to journalArticle

96 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)65-75
Number of pages11
JournalCancer Cell
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

Fingerprint

Neurofibromatoses
Schwann Cells
Peripheral Nerves
Epidermal Growth Factor Receptor
Carcinogenesis
Neurofibroma
Transgenic Mice
Hemizygote
Peripheral Nervous System Neoplasms
Neurofibromatosis 1
Neurilemmoma
Mast Cells
Sarcoma
Hyperplasia
Axons
Collagen
Phenotype

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Role for the epidermal growth factor receptor in neurofibromatosis-related peripheral nerve tumorigenesis. / Ling, Benjamin C.; Wu, Jianqiang; Miller, Shyra J.; Monk, Kelly; Shamekh, Rania; Rizvi, Tilat A.; Decourten-Myers, Gabrielle; Vogel, Kristine S.; Declue, Jeffrey E.; Ratner, Nancy.

In: Cancer Cell, Vol. 7, No. 1, 01.01.2005, p. 65-75.

Research output: Contribution to journalArticle

Ling, BC, Wu, J, Miller, SJ, Monk, K, Shamekh, R, Rizvi, TA, Decourten-Myers, G, Vogel, KS, Declue, JE & Ratner, N 2005, 'Role for the epidermal growth factor receptor in neurofibromatosis-related peripheral nerve tumorigenesis', Cancer Cell, vol. 7, no. 1, pp. 65-75. https://doi.org/10.1016/j.ccr.2004.10.016
Ling, Benjamin C. ; Wu, Jianqiang ; Miller, Shyra J. ; Monk, Kelly ; Shamekh, Rania ; Rizvi, Tilat A. ; Decourten-Myers, Gabrielle ; Vogel, Kristine S. ; Declue, Jeffrey E. ; Ratner, Nancy. / Role for the epidermal growth factor receptor in neurofibromatosis-related peripheral nerve tumorigenesis. In: Cancer Cell. 2005 ; Vol. 7, No. 1. pp. 65-75.
@article{eb6a6d31a0d846f3bcb377fc8ae86b88,
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 Kelly Monk and Rania Shamekh and Rizvi, {Tilat A.} and Gabrielle Decourten-Myers and Vogel, {Kristine S.} and Declue, {Jeffrey E.} and Nancy Ratner",
year = "2005",
month = "1",
day = "1",
doi = "10.1016/j.ccr.2004.10.016",
language = "English (US)",
volume = "7",
pages = "65--75",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Role for the epidermal growth factor receptor in neurofibromatosis-related peripheral nerve tumorigenesis

AU - Ling, Benjamin C.

AU - Wu, Jianqiang

AU - Miller, Shyra J.

AU - Monk, Kelly

AU - Shamekh, Rania

AU - Rizvi, Tilat A.

AU - Decourten-Myers, Gabrielle

AU - Vogel, Kristine S.

AU - Declue, Jeffrey E.

AU - Ratner, Nancy

PY - 2005/1/1

Y1 - 2005/1/1

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.

UR - http://www.scopus.com/inward/record.url?scp=19944430338&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=19944430338&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2004.10.016

DO - 10.1016/j.ccr.2004.10.016

M3 - Article

VL - 7

SP - 65

EP - 75

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 1

ER -