c-Myc promoter activation in medulloblastoma

• Published in: Cancer research (Chicago, Ill.) Ill.), 2003-08, Vol.63 (16), p.4773-4776
• Main Authors: SIU, I-Mei, LAL, Anita, BLANKENSHIP, Jill R, ALDOSARI, Naji, RIGGINS, Gregory J
• Format: Article
• Language: English
• Subjects: b-catenin; Base Sequence; beta Catenin; Binding Sites; Biological and medical sciences; c-myc gene; Cytoskeletal Proteins - metabolism; Gene Expression Regulation, Neoplastic; General aspects (metabolism, cell proliferation, established cell line...); Genes, myc; Humans; Medical sciences; medulloblastoma; Medulloblastoma - genetics; Molecular Sequence Data; Promoter Regions, Genetic; Trans-Activators - metabolism; Tumor cell; Tumor Cells, Cultured; Tumors
• ISSN: 0008-5472; 1538-7445

%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.