Ras-GTP levels are elevated in human NF1 peripheral nerve tumors

A. Guha, N. Lau, I. Huvar, D. Gutmann, J. Provias, T. Pawson, G. Boss

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

Neurofibromin, the gene product of NF1, is a Ras GTPase Activating Protein. The absence of neurofibromin leads to increased levels of Ras-GTP, which contributes to the proliferation of NF1 neurogenic sarcoma cell lines. Whether this pathogenic mechanism is applicable to benign and malignant peripheral nerve tumours from NF1 and non NF1 patients is not known, due to lack of a tissue based assay. We have adapted a colorimetric enzymatic assay for determining levels of Ras bound guanine nucleotides in tissues. Ras-GTP levels were increased in NF1 neurogenic sarcomas (15 times) and benign NF1 neurofibromas (four times), compared to non NF1 schwannomas. Neurofibromin was not expressed in NF1 sarcomas, in support of its important negative Ras regulatory role in the pathogenesis of NF1 peripheral nerve tumors.

Original languageEnglish
Pages (from-to)507-513
Number of pages7
JournalOncogene
Volume12
Issue number3
StatePublished - 1996

Keywords

  • NF1
  • Ras
  • Ras-GDP

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