ArticleThe Journal of biological chemistry2000
Single cell Ras-GTP analysis reveals altered Ras activity in a subpopulation of neurofibroma Schwann cells but not fibroblasts.
Article in The Journal of biological chemistry, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03231306 (A Phase II Study of Binimetinib in Children and Adults With NF1 Associated Plexiform Neurofibromas), which is not on this map. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase II Study of Binimetinib in Children and Adults With NF1 Associated Plexiform Neurofibromas (PNOC010)
Who cites it
48 citing papers in PubMed, 139 citations in OpenAlex.
- MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors.The Journal of clinical investigation · 2013Trial
- Galectin-1 Inhibition as a Strategy for Malignant Peripheral Nerve Sheath Tumor Treatment.Cells · 2025Article
- Granulocyte-Macrophage Colony Stimulating Factor Receptor Contributes to Plexiform Neurofibroma Initiation.Cancers · 2025Article
- Targeting the Galectin-1/Ras Interaction for Treating Malignant Peripheral Nerve Sheath Tumors.Research square · 2024Article
- Unbalancing cAMP and Ras/MAPK pathways as a therapeutic strategy for cutaneous neurofibromas.JCI insight · 2024Article
- Article
- AfterNeuro-oncology advances · 2020Review
- Galectin-1 inhibition induces cell apoptosis through dual suppression of CXCR4 and Ras pathways in human malignant peripheral nerve sheath tumors.Neuro-oncology · 2019Article
- Article
- Cutaneous neurofibromas in the genomics era: current understanding and open questions.British journal of cancer · 2018Review
- Immunohistochemical Markers for Prospective Studies in Neurofibromatosis-1 Porcine Models.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2017Article
- KIR2DL5 mutation and loss underlies sporadic dermal neurofibroma pathogenesis and growth.Oncotarget · 2017Article
- Comprehensive establishment and characterization of orthoxenograft mouse models of malignant peripheral nerve sheath tumors for personalized medicine.EMBO molecular medicine · 2015Article
- Translationally controlled tumor protein is a novel biological target for neurofibromatosis type 1-associated tumors.The Journal of biological chemistry · 2014Article
- Trp53 haploinsufficiency modifies EGFR-driven peripheral nerve sheath tumorigenesis.The American journal of pathology · 2014Article
- Forward genetic screen for malignant peripheral nerve sheath tumor formation identifies new genes and pathways driving tumorigenesis.Nature genetics · 2013Article
- Phase I trial and pharmacokinetic study of sorafenib in children with neurofibromatosis type I and plexiform neurofibromas.Pediatric blood & cancer · 2013Article
- Ras-driven transcriptome analysis identifies aurora kinase A as a potential malignant peripheral nerve sheath tumor therapeutic target.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Article
- Oncogenic Kras expression in postmitotic neurons leads to S100A8-S100A9 protein overexpression and gliosis.The Journal of biological chemistry · 2012Article
- Molecular mechanisms promoting the pathogenesis of Schwann cell neoplasms.Acta neuropathologica · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Neurofibromatosis type 1 (NF1) is a common genetic disorder characterized by multiple neurofibromas, peripheral nerve tumors containing mainly Schwann cells and fibroblasts. The NF1 gene encodes neurofibromin, a tumor suppressor postulated to function in part as a Ras GTPase-activating protein. The roles of different cell types and of elevated Ras-GTP in neurofibroma formation are unclear. To determine which neurofibroma cell type has altered Ras-GTP regulation, we developed an immunocytochemical assay for active, GTP-bound Ras. In NIH 3T3 cells, the assay detected overexpressed, constitutively activated K-, N-, and Ha-Ras and insulin-induced endogenous Ras-GTP. In dissociated neurofibroma cells from NF1 patients, Ras-GTP was elevated in Schwann cells but not fibroblasts. Twelve to 62% of tumor Schwann cells showed elevated Ras-GTP, unexpectedly revealing neurofibroma Schwann cell heterogeneity. Increased basal Ras-GTP did not correlate with increased cell proliferation. Normal human Schwann cells, however, did not demonstrate elevated basal Ras activity. Furthermore, compared with cells from wild type littermates, Ras-GTP was elevated in all mouse Nf1(-/-) Schwann cells but never in Nf1(-/-) mouse fibroblasts. Our results indicate that Ras activity is detectably increased in only some neurofibroma Schwann cells and suggest that neurofibromin is not an essential regulator of Ras activity in fibroblasts.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.