Aberrant Gene Expression in NF1-Mediated Oncogenesis
Annual rept. 1 Sep 2000-31 Aug 2002
NORTH CAROLINA UNIV AT CHAPEL HILL
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Recent genetic understanding has identified the gene NFl to be disrupted or mutated in patients affected with NFl resulting in reduced expression of the protein neurofibromin. One function if NFl has shown that it acts to negatively regulate, or turn off positive signals in the cell that direct the cell to proliferate. Specifically, NFl turns the positive signals relayed by a protein called Ras. However, other studies have shown that NFl may negatively regulate cell proliferation by mechanisms other than through inactivation of Ras. These other mechanisms however are currently unknown. The purpose of the proposed study was to determine what changes in gene expression occur in cells from a patient with neurofibromatosis when we force these cells to express neurofibromin. The study was designed to identify and determine genes deregulated by NF I in a Ras-dependent and Ras-independent manner. Taken together, these studies were designed to contribute to our understanding of the function and downstream effects NFl has on the cell. In addition, determining the downstream nuclear events that occur in response to NFl may provide novel targets for the treatment of NFl associated cancers.
- Medicine and Medical Research