Poster Sessions AP05: Neuronal and Glial Cell Biology. Novel roles for acetylcholinesterase in brain tumors

Abstract

Acetylcholinesterase (AChE) is classically known for terminating cholinergic transmission, however, increasing evidence shows that the biological function of AChE is not limited to this role. Interestingly, the AChE gene is either amplified, mutated and/or aberrantly expressed by cells in a variety of human tumors despite the fact that AChE is not present in their normal counterparts. Studies from our laboratory and others have shown that AChE is transiently expressed during normal neural development when cells are invariably engaged in intense growth and movement. Together, these observations support the idea that AChE may play a role in tumorigenesis, however, this hypothesis has not been tested before. In support of this idea, we have found that neuroblastoma cells genetically engineered to over‐express AChE developed tumors in vivo at a notably greater rate compared with transfection controls. Tumor cells were implanted into the brains of irradiated Fischer rats and following a 10‐day survival period, macroscopic examination revealed that the tumor mass generated from the AChE over‐expressing cells was six‐fold greater than transfection controls. Moreover, histochemical and Western blot analyses of two human glioma cell lines revealed that the different levels of AChE expression in these cells directly correlated with their proliferation rates. These studies showed that the high AChE‐expressing cells divided at a 50% greater rate than the low AChE‐expressing cells. Interestingly, the high AChE‐expressing cells also exhibited increased MAPK phosphorylation, a key step in the regulation of cell growth. These findings together with the consistent observation that AChE is misexpressed in human tumors, and the fact that AChE levels are up‐regulated during normal development, support the idea that AChE plays a role in tumor cell growth.