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

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

doi:10.1016/j.ccr.2004.10.016

Cited by 114 publications

(141 citation statements)

References 49 publications

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“…We believe that the Ctv-a mouse may also be a useful model for studies of the peripheral nervous system because the Cnp promoter also targets Schwann cells (Gravel et al, 1998). In a recently described transgenic mouse model of neurofibroma, expression of the human epidermal growth factor receptor (hEGFR) was directed to CNP-expressing Schwann cells (Ling et al, 2005). These mice developed Schwann cell hyperplasias but showed no signs of glioma development, which was explained by the lack of EGFR ligands in the brain.…”

Section: Discussionmentioning

confidence: 99%

Oligodendrocyte progenitor cells can act as cell of origin for experimental glioma

et al. 2009

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Gliomas are primary brain tumors mainly affecting adults. The cellular origin is unknown. The recent identification of tumor-initiating cells in glioma, which share many similarities with normal neural stem cells, has suggested the cell of origin to be a transformed neural stem cell. In previous studies, using the RCAS/tv-a mouse model, platelet-derived growth factor B (PDGF-B)-induced gliomas have been generated from nestin or glial fibrillary acidic protein-expressing cells, markers of neural stem cells. To investigate if committed glial progenitor cells could be the cell of origin for glioma, we generated the Ctv-a mouse where tumor induction would be restricted to myelinating oligodendrocyte progenitor cells (OPCs) expressing 2 0 ,3 0 -cyclic nucleotide 3 0 -phosphodiesterase. We showed that PDGF-B transfer to OPCs could induce gliomas with an incidence of 33%. The majority of tumors resembled human WHO grade II oligodendroglioma based on close similarities in histopathology and expression of cellular markers. Thus, with the Ctv-a mouse we have showed that the cell of origin for glioma may be a committed glial progenitor cell.

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Section: Discussionmentioning

confidence: 99%

Oligodendrocyte progenitor cells can act as cell of origin for experimental glioma

et al. 2009

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“…98 Although the EGF receptor is in the same family as the NRG1 receptors, the phenotype of Cnp-hEGFR mice is more subtle than that of P 0 -GGFb3 mice. Cnp-hEGFR mice show Schwann cell hyperplasia, dissociation of Schwann cells from axons, increased numbers of intraneural mast cells, and fibrosis, but frank neurofibroma formation is rare, indicating that inappropriate expression of the EGF receptor is not sufficient for tumorigenesis.…”

Section: Currently Available Mouse Models Of Neurofibroma and Mpnst Pmentioning

confidence: 99%

The Challenge of Cancer Genomics in Rare Nervous System Neoplasms

Carroll

2016

The American Journal of Pathology

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Comprehensive genomic analyses of common nervous system cancers provide new insights into their pathogenesis, diagnosis, and treatment. Although analogous studies of rare nervous system tumors are needed, there are major barriers to performing such studies. Cross-species comparative oncogenomics, identifying driver mutations in mouse cancer models and validating them in human tumors, is a promising alternative. Although still in its infancy, this approach is being applied to malignant peripheral nerve sheath tumors (MPNSTs), rare Schwann cellederived malignancies that occur sporadically, after radiotherapy, and in neurofibromatosis type 1. Studies of human neurofibromatosis type 1eassociated tumors suggest that NF1 tumor suppressor loss in Schwann cells triggers cell-autonomous and intercellular changes, resulting in development of benign neurofibromas; subsequent neurofibroma-MPNST progression is caused by aberrant growth factor signaling and mutations affecting the p16 INK4A -cyclin D1-CDK4-Rb and p19 ARF -Mdm2-p53 cell cycle pathways. Mice with Nf1, Trp53, and/or Cdkn2a mutations that overexpress the Schwann cell mitogen neuregulin-1 or overexpress the epidermal growth factor receptor validate observations in human tumors and, to various degrees, model human tumorigenesis. Genomic analyses of MPNSTs arising in neuregulin-1 and epidermal growth factor receptor-overexpressing mice and forward genetic screens with Sleeping Beauty transposons implicate additional signaling cascades in MPNST pathogenesis. These studies confirm the utility of mouse models for MPNST driver gene discovery and provide new insights into the complexity of MPNST pathogenesis. (Am J Pathol 2016, 186: 464e477; http://dx

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“…The generation and characterization of the CNP-EGFP mouse has been previously described (Yuan et al, 2002) Details on the generation and characterization of the CNP-hEGFR transgenic mice have been previously reported (Ling et al, 2005). Genotyping of these transgenic mice was performed by PCR.…”

Section: Transgenic and Mutant Micementioning

confidence: 99%

“…We have recently utilized a CNP-hEGFR mouse, in which the human EGFR is overexpressed in neural progenitors that express the CNP gene (Ling et al, 2005;Aguirre et al, 2005;Aguirre et al, 2007). We showed that OPCs that express the membrane proteoglycan NG2 also display EGFR signaling .…”

Section: Introductionmentioning

confidence: 99%

Reduced EGFR signaling in progenitor cells of the adult subventricular zone attenuates oligodendrogenesis after demyelination

Aguirre

Gallo

2007

Neuron Glia Biol.

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Neural progenitor cells expressing the NG2 proteoglycan are found in different regions of the adult mammalian brain, where they display distinct morphologies and proliferative rates. In the developing postnatal and adult mouse, NG2 + cells represent a major cell population of the subventricular zone (SVZ). NG2 + cells divide in the anterior and lateral region of the SVZ, and are stimulated to proliferate and migrate out of the SVZ by focal demyelination of the corpus callosum (CC). Many NG2 + cells are labeled by GFP-retrovirus injection into the adult SVZ, demonstrating that NG2 + cells actively proliferate under physiological conditions and after demyelination. In the wa2 mouse, which is characterized by reduced EGFR signaling, NG2 + cell proliferation, under normal physiological conditions and after focal demyelination, is significantly attenuated. This results in reduced SVZ-to-lesion migration of NG2 + cells and oligodendrogenesis in the lesion. Expression of VEGF and EGFR ligands, such as HB-EGF and TGF-alpha, is upregulated in the SVZ after focal demyelination of the CC. EGF-induced oligodendrogenesis and myelin protein expression in cultured wild-type SVZ cells were significantly attenuated in wa2 SVZ cells. Our results demonstrate that the NG2 + cell response in the SVZ and their subsequent differentiation in CC after focal demyelination are dependent upon EGFR signaling.

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

Cited by 114 publications

References 49 publications

Oligodendrocyte progenitor cells can act as cell of origin for experimental glioma

Oligodendrocyte progenitor cells can act as cell of origin for experimental glioma

The Challenge of Cancer Genomics in Rare Nervous System Neoplasms

Reduced EGFR signaling in progenitor cells of the adult subventricular zone attenuates oligodendrogenesis after demyelination

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