title: c-Myc promoter activation in medulloblastoma.
abstract: %The c-myc oncogene is commonly activated in medulloblastoma. Genomic amplification is a well-documented cause of c-myc activation but does not account for all cases of c-myc activation. In this study, we sought other means by which c-myc is overexpressed in medulloblastoma. Twelve medulloblastoma or PNET cell lines were screened for c-myc genomic amplification, mRNA levels, and protein levels. Two medulloblastoma lines, D283 Med and D721 Med, were identified that expressed c-myc mRNA and protein at high levels without genomic amplification. The c-myc gene's regulatory sequences were normal in those cell lines. However, specific regions of the promoter, independent of the beta-catenin binding sites, were responsible for activation as revealed by promoter assays and site-directed mutagenesis. Transcriptional activation by a beta-catenin-independent pathway is therefore a likely mechanism for c-myc overexpression in a subset of medulloblastomas.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: I-Mei
authors.initials: IM
authors.lastname: Siu
authors.forename: Anita
authors.initials: A
authors.lastname: Lal
authors.forename: Jill R
authors.initials: JR
authors.lastname: Blankenship
authors.forename: Naji
authors.initials: N
authors.lastname: Aldosari
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riggins
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D003598:Cytoskeletal Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin