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. Clapp, George H. De Vries

Research output: Contribution to journalArticle

14 Citations (Scopus)

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

Fingerprint

Neurofibromin 1
Neurofibromatosis 1
Schwann Cells
Cells
Tumors
Chemical activation
Nerve Sheath Neoplasms
Neurilemmoma
Growth
Phenotype
Proteins

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Thomas, S. L., Deadwyler, G. D., Tang, J., Stubbs, E. B., Muir, D., Hiatt, K. K., ... 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

Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells. / Thomas, Stacey L.; Deadwyler, Gail D.; Tang, Jun; Stubbs, Evan B.; Muir, David; Hiatt, Kelly K.; Clapp, D.; De Vries, George H.

In: Biochemical and Biophysical Research Communications, Vol. 348, No. 3, 29.09.2006, p. 971-980.

Research output: Contribution to journalArticle

Thomas, SL, Deadwyler, GD, Tang, J, Stubbs, EB, Muir, D, Hiatt, KK, Clapp, D & De Vries, GH 2006, 'Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells', Biochemical and Biophysical Research Communications, vol. 348, no. 3, pp. 971-980. https://doi.org/10.1016/j.bbrc.2006.07.159
Thomas, Stacey L. ; Deadwyler, Gail D. ; Tang, Jun ; Stubbs, Evan B. ; Muir, David ; Hiatt, Kelly K. ; Clapp, D. ; De Vries, George H. / Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells. In: Biochemical and Biophysical Research Communications. 2006 ; Vol. 348, No. 3. pp. 971-980.
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