Proliferation-associated Brn-3b transcription factor can activate cyclin D1 expression in neuroblastoma and breast cancer cells

Oncogene. 2008 Jan 3;27(1):145-54. doi: 10.1038/sj.onc.1210621. Epub 2007 Jul 16.

Abstract

Brn-3b transcription factor enhances proliferation of neuroblastoma (NB) and breast cancer cell lines in vitro and increases the rate and size of in vivo tumour growth, whereas reducing Brn-3b slows growth, both in vitro and in vivo. Brn-3b is elevated in >65% of breast cancer biopsies, and here we demonstrate that Brn-3b is also elevated in NB tumours. We show a significant correlation between Brn-3b and cyclin D1 (CD1) in breast cancers and NB tumours and cell lines. Brn-3b directly transactivates the CD1 promoter in co-transfection experiments, whereas electrophoretic mobility shift assay and chromatin immunoprecipitation assays demonstrate that Brn-3b protein binds to an octamer sequence located in the proximal CD1 promoter. Site-directed mutagenesis of this sequence resulted in loss of transactivation of the CD1 promoter by Brn-3b. Thus, Brn-3b may act to alter growth properties of breast cancer and NB cells by enhancing CD1 expression in these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cyclin D1 / biosynthesis
  • Cyclin D1 / genetics*
  • Cyclin D1 / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / metabolism
  • Transcription Factor Brn-3B / biosynthesis
  • Transcription Factor Brn-3B / genetics
  • Transcription Factor Brn-3B / physiology*
  • Transcriptional Activation*
  • Tumor Cells, Cultured
  • Up-Regulation / physiology

Substances

  • RNA, Messenger
  • Transcription Factor Brn-3B
  • Cyclin D1