title: Alterations in the rap1 signaling pathway are common in human gliomas.
abstract: Several inherited predisposition to cancer syndromes are associated with the development of nervous system tumors. Tuberous sclerosis complex (TSC) is an autosomal dominant disorder in which affected individuals are at risk for developing astrocytomas. One of the genes responsible for this disorder is TSC2, located on chromosome 16p, and encoding a 180 kDa protein (tuberin) that functions in part as a negative regulator of rap1. Previous studies from our laboratory demonstrated that 30% of sporadic astrocytomas have reduced or absent tuberin expression. In addition to loss of tuberin in sporadic astrocytomas, aberrant rap1 mediated signaling may also result from overexpression of rap1. In this study, we test the hypothesis that alterations in the rap1 signaling pathway are frequently observed in certain subsets of gliomas compared to other tumors of the nervous system. Analysis of sporadic astrocytomas and ependymomas demonstrated either increased rap1 or reduced/absent tuberin protein expression in 50-60% of different cohorts of these gliomas, compared to 30-33% of sporadic schwannomas and meningiomas and none of eight oligodendrocyte tumors. These results suggest that alterations in the rap1 signaling pathway are important in the development of certain sporadic human gliomas.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Gutmann
authors.forename: S
authors.initials: S
authors.lastname: Saporito-Irwin
authors.forename: J E
authors.initials: JE
authors.lastname: DeClue
authors.forename: R
authors.initials: R
authors.lastname: Wienecke
authors.forename: A
authors.initials: A
authors.lastname: Guha
mesh_terms: D000328:Adult; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D008579:Meningioma / Q000378:metabolism; D009442:Neurilemmoma / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins / Q000378:metabolism; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D020668:rap GTP-Binding Proteins
chemical_list: D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D019204:GTP-Binding Proteins; D020668:rap GTP-Binding Proteins