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

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.

• Authors: V S Budhram-Mahadeo, S Irshad, S Bowen, S A Lee, L Samady, G P Tonini, D S Latchman
• Journal: Oncogene (Oncogene) Vol. 27 Issue 1 Pg. 145-54 (Jan 03 2008) ISSN: 1476-5594 [Electronic] England
• PMID: 17637757 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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