Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells

Stacey L. Thomas, Gail D. Deadwyler, Jun Tang, Evan B. Stubbs, David Muir, Kelly K. Hiatt, D. Wade Clapp, George H. De Vries

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Schwann cells derived from peripheral nerve sheath tumors from individuals with Neurofibromatosis Type 1 (NF1) are deficient for the protein neurofibromin, which contains a GAP-related domain (NF1-GRD). Neurofibromin-deficient Schwann cells have increased Ras activation, increased proliferation in response to certain growth stimuli, increased angiogenic potential, and altered cell morphology. This study examined whether expression of functional NF1-GRD can reverse the transformed phenotype of neurofibromin-deficient Schwann cells from both benign and malignant peripheral nerve sheath tumors. We reconstituted the NF1-GRD using retroviral transduction and examined the effects on cell morphology, growth potential, and angiogenic potential. NF1-GRD reconstitution resulted in morphologic changes, a 16-33% reduction in Ras activation, and a 53% decrease in proliferation in neurofibromin-deficient Schwann cells. However, NF1-GRD reconstitution was not sufficient to decrease the in vitro angiogenic potential of the cells. This study demonstrates that reconstitution of the NF1-GRD can at least partially reverse the transformation of human NF1 tumor-derived Schwann cells.

Original languageEnglish (US)
Pages (from-to)971-980
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume348
Issue number3
DOIs
StatePublished - Sep 29 2006

Keywords

  • Angiogenesis
  • Morphology
  • MPNST
  • Neurofibroma
  • Neurofibromatosis
  • NF1
  • NF1-GRD
  • Proliferation
  • Ras
  • Schwann cell

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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    Thomas, S. L., Deadwyler, G. D., Tang, J., Stubbs, E. B., Muir, D., Hiatt, K. K., Clapp, D. W., & De Vries, G. H. (2006). Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells. Biochemical and Biophysical Research Communications, 348(3), 971-980. https://doi.org/10.1016/j.bbrc.2006.07.159