Addiction of MYCN amplified tumours to B-MYB underscores a reciprocal regulatory loop

Oncotarget. 2010 Aug;1(4):278-288. doi: 10.18632/oncotarget.138.


MYCN is a member of the MYC family of oncoproteins frequently amplified or overexpressed in aggressive, paediatric tumours of the nervous system. In this study we have identified the gene B-MYB, encoding the transcription factor also known as MYBL2, as a downstream target of MYCN. Using multiple in silico databases we show that expression of B-MYB significantly correlates with that of MYCN in neuroblastoma patients. MYCN binds to and activates the B-MYB gene in vivo and in vitro. Blunting B-MYB expression by RNA interference causes reduced proliferation of MYCN amplified, but not MYCN-non amplified, neuroblastoma cell lines, indicating that tumour cells are addicted to B-MYB in a MYCN dependent manner. Notably, B-MYB binds in vivo to the MYCN amplicon and is required for its expression. We conclude that MYCN and B-MYB are engaged in a reciprocal regulatory loop whose pharmacological targeting could be beneficial to patients with the aggressive forms of cancer in which MYCN is amplified.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Chromatin Immunoprecipitation
  • Gene Expression
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • N-Myc Proto-Oncogene Protein
  • Neuroblastoma / genetics*
  • Neuroblastoma / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • RNA Interference
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism


  • Cell Cycle Proteins
  • MYBL2 protein, human
  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Oncogene Proteins
  • Trans-Activators