The Role of RASGRF1 in Neurofibromatosis-Validating a Potential Therapeutic Target
Abstract
It is hypothesized that the gene encoding RASGRF1p07, a GTP exchange factor (GEF), controls the severity of neurofibromatosis. Over-expression of Rasgd1 is predicted to exacerbate neurofibromatosis while Rasgd1 silencing will attenuate it. Two novel strains of mice ideally suited to test this hypothesis that were developed in my lab are being used to evaluate the role or Rasgd1 on the manifestations of neurofibromatosis type 1. One strain of mice over-express Rasgif1, the other has diminished expression. These were crossed with a mouse model for NF1 and the effects of the altered level of RASGRFI on tumorigenesis were monitored. The results indicate that over-expression of Rasgd1 significantly hastens the time of tumor onset and increases the overall frequency of tumor incidence. In contrast, diminished expression modestly delays the timing of tumor development, but overall frequency of tumor development is not changed. To extend this work from the genetic to biochemical, we have established assays to evaluate Ras activation status. The analysis of tumors and tissues from mice is ongoing. To extend this work further from mouse to human, we are establishing the assays to detect human RASGRF1 mRNA from human tumor sections using in situ hybridization.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2005
- Accession Number
- ADA448171
Entities
People
- Paul D. Soloway
Organizations
- Cornell University