Aberrant Gene Expression in NF1-Mediated Oncogenisis

摘要

Recent genetic understanding has identified the gene NF1 to be disrupted or mutated in patients affected with NF1 resulting in reduced expression of the protein neurofibromin. One function of NF1 has shown that it acts to negatively regulate, or turn off, positive signals in the cell that direct the cell to proliferate. Specifically, NF1 turn the positive signals relayed by a protein called Ras. However, other studies have shown that NF1 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 NF1 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 NF1 has on the cell. In addition, determining the downstream nuclear events that occur in response to NF1 may provide novel targets for the treatment of NF1 associated cancers.