Neurofibromatosis 2

Baser, Michael E.; Evans, D Gareth; Gutmann, David H.

doi:10.1097/00019052-200302000-00004

Cited by 121 publications

(77 citation statements)

References 53 publications

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“…Muscle precursors can apparently undergo epithelial to mesenchymal transitions normally, in the presence of ectopic merlin. Previous studies have supported a role for merlin in regulating cell proliferation (Sherman et al, 1997;Ikeda et al, 1999;Giovannini et al, 2000;Baser et al, 2003). Our results indicate that c-merlin can also act as a negative regulator of cell proliferation during chicken embryonic development and furthermore, that c-merlin acts to inhibit cell migration.…”

Section: Discussionsupporting

confidence: 80%

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Characterization of chicken Nf2/merlin indicates regulatory roles in cell proliferation and migration

Chen

Gutmann

Haipek

et al. 2004

Developmental Dynamics

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The neurofibromatosis 2 (NF2) tumor suppressor protein merlin, or schwannomin, functions as a negative growth regulator such that inactivating mutations in Nf2 predispose humans to tumors. In addition, merlin has a critical role during embryonic development. Nf2-deficient mice die early during embryogenesis, with defects in gastrulation and extraembryonic tissues. To investigate the function of Nf2/merlin during embryonic development, we first identified the homologous Nf2 gene in chicken (cNf2) and examined the distribution of chicken merlin (c-merlin) during myogenesis. cNf2 encoded a full-length mRNA of 1,770 nucleotides and a protein of 589 residues. C-merlin shared high sequence homology and common protein motifs with vertebrate and Drosophila merlins. In addition, cNF2 functions as a negative growth regulator similar to human and Drosophila merlin in vitro. In vivo, c-merlin was expressed diffusely in the forming dermomyotome but down-regulated in migratory muscle precursors in the forelimb. As muscle formed in the limb, c-merlin expression was up-regulated. As an initial examination of c-merlin function during myogenesis, c-merlin was ectopically expressed in muscle precursors and the effects on muscle development were examined. We show that ectopic merlin expression reduces the proliferation of muscle precursors as well as their ability to migrate effectively in limb mesoderm. Collectively, these results demonstrate that c-merlin is developmentally regulated in migrating and differentiating myogenic cells, where it functions as a negative regulator of both muscle growth and motility. Developmental Dynamics 229:541-554, 2004.

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Section: Discussionsupporting

confidence: 80%

“…First, Nf2 inactivation and loss of merlin expression has been demonstrated in all NF2-associated tumors examined as well as a significant proportion of sporadic schwannomas, meningiomas, and ependymomas (reviewed in Baser et al, 2003). Second, re-expression of wild-type merlin, but not merlincontaining NF2 patient mutations, in…”

Section: Introductionmentioning

confidence: 99%

Characterization of chicken Nf2/merlin indicates regulatory roles in cell proliferation and migration

Chen

Gutmann

Haipek

et al. 2004

Developmental Dynamics

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“…Mutations in the NF2 gene predispose to tumors of the nervous system, mainly schwannomas and meningiomas (Baser et al, 2003). The NF2 gene encodes the tumor suppressor protein merlin (or schwannomin), which shares overall structural similarity with the highly conserved ERM (ezrin-radixin-moesin) family of proteins (Rouleau et al, 1993;Trofatter et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Protein kinase A-mediated phosphorylation of the NF2 tumor suppressor protein merlin at serine 10 affects the actin cytoskeleton

et al. 2007

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“…1,2 Schwannomas can arise during development, as Schwann cells move out along axons and begin myelination, or later in life when Schwann cells dedifferentiate and commence proliferation in response to nerve injury. 3 In fact, Schwann cells in damaged nerves share many features with Schwann cells in development.…”

Section: Introductionmentioning

confidence: 99%

Treatment of Implantable NF2 Schwannoma Tumor Models with Oncolytic Herpes Simplex Virus G47Δ

et al. 2007

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Schwannomas are benign tumors composed of dedifferentiated Schwann cells that form along peripheral nerves causing nerve compression often associated with pain and loss of function. Current surgical therapy involves total or subtotal surgical removal of the tumor, which may cause permanent nerve damage. In the present study, we explore an alternate means of therapy in which schwannomas are injected with a replication-conditional herpes simplex virus (HSV) vector to shrink the tumor through cell lysis during virus propagation. The oncolytic vector used, G47D, has deletions in HSV genes, which allow it to replicate selectively in dividing cells, sparing neurons. Two schwannoma cell lines were used to generate subcutaneous tumors in nude mice: HEI193, an immortalized human line previously established from an NF2 patient and NF2S-1, a newly generated spontaneous mouse line. Subcutaneous HEI193 tumors grew about ten times as fast as NF2S-1 tumors, and both regressed substantially following injection of G47D. Complete regression of HEI193 tumors was achieved in most animals, whereas all NF2S-1 tumors resumed growth within 2 weeks after vector injection. These studies provide a new schwannoma model for testing therapeutic strategies and demonstrate that oncolytic HSV vectors can be successfully used to shrink growing schwannomas.

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Neurofibromatosis 2

Cited by 121 publications

References 53 publications

Characterization of chicken Nf2/merlin indicates regulatory roles in cell proliferation and migration

Characterization of chicken Nf2/merlin indicates regulatory roles in cell proliferation and migration

Protein kinase A-mediated phosphorylation of the NF2 tumor suppressor protein merlin at serine 10 affects the actin cytoskeleton

Treatment of Implantable NF2 Schwannoma Tumor Models with Oncolytic Herpes Simplex Virus G47Δ

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