Molecular Mechanisms of Schwann Cell Proliferation in NF1
Abstract
Using Schwann cell lines derived from neurofibromatosis (NF) patients, primary human Schwann cells, and a Schwann cell line derived from a non-NF patient, we report metabolic changes leading to chronic proliferation of NF-derived Schwann cells. The growth factor receptors c-Kit and PDGF are overexpressed while the erb B3 receptor is absent in the NF-derived cell lines. Excess arachidonate metabolism results in the secretion of thromboxane and prostaglandins; as a consequence the basal levels of intracellular cAMP are at least 10-fold elevated in the NF-derived Schwann cells. Taken as a whole, this data leads to the following metabolic scheme which is consistent with hyperproliferation and tumor formation in NF-1 patients. MAP kinase is activated via the overexpressed growth factor receptors as well as RAS pathway which is activated as a consequence of the absent neurofibromin. The hyperstimulated MAP kinase phosphorylates and activates phospholipase A2 which releases arachidonate metabolites causing the chronic elevation of cAMP which in turn sustains the overproduction of growth factor receptors. In this manner, a self-sustaining, hyperproliferative state is attained which is characteristic of NF-1. Further experiments are in progress to confirm these molecular mechanisms of Schwann cell proliferation in NF-1.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA385683
Entities
People
- George H. Devries
Organizations
- Chicago Association for Research and Education in Science