Molecular Mechanisms of Schwann Cell Proliferation in NF1

摘要

Neurofibromatosis type 1 (NFl) is a genetic disorder characterized by tumors comprised principally of Schwann cells lacking the neurofibromin gene. Our studies concentrated on the metabolic changes that occur in Schwann cells derived from NFl tumors. We documented the following changes: aberrant expression of cell surface receptors, including c-Kit and pDGF, novel pathways stimulated by activation of these receptors leading to the prevention of apoptosis and increased calcium levels, abnormal secretion of prostaglandin, and subsequent activation of prostaglandin receptors, increased expression of prostaglandin receptors, and elevated cAMP. Developmental studies of c-Kit revealed the role for this cell surface receptor during development in preventing apoptosis. The overexpression of these receptors and subsequent changes in intracellular metabolism all contribute to the enhancement of the proliferative potential of Schwann cells, allowing increased tumor growth. These altered metabolic pathways provide new therapeutic targets for controlling the growth of Schwann cells in tumors in neurofibromatosis type 1.