c-Myc promoter activation in medulloblastoma

Cancer Res. 2003 Aug 15;63(16):4773-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cytoskeletal Proteins / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Genes, myc*
  • Humans
  • Medulloblastoma / genetics*
  • Molecular Sequence Data
  • Promoter Regions, Genetic*
  • Trans-Activators / metabolism
  • Tumor Cells, Cultured
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin