화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.348, No.3, 971-980, 2006
Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells
Schwann cells derived from peripheral nerve sheath tumors from individuals with Neurofibromatosis Type I (NF1) are deficient for the protein neurofibromin, which contains a GAP-related domain (NF1-GRD). Neurofibromin-deficient Schwarm 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 Schwarm 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 NFI-GRD can at least partially reverse the transformation of human NEI tumor-derived Schwarm cells. Published by Elsevier Inc.