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

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.

The Brn-3b POU family transcription factor represses plakoglobin gene expression in human breast cancer cells.

The Brn-3b transcription factor has been shown to be overexpressed in human breast cancer cells and contributes toward cell growth regulation. Using micro-arrays, more than 50 cancer-related genes regulated by Brn-3b in human breast cancer cells have been identified. For example, Brn-3b activates the cell cycle regulator CDK4 that provides a mechanism by which Brn-3b controls the growth of breast cancer cells.

Expression of the Brn-3b transcription factor correlates with expression of HSP-27 in breast cancer biopsies and is required for maximal activation of the HSP-27 promoter.

In breast cancer, overexpression of the small heat shock protein, HSP-27, is associated with increased anchorage-independent growth, increased invasiveness, and resistance to chemotherapeutic drugs and is associated with poor prognosis and reduced disease-free survival. Therefore, factors that increase the expression of HSP-27 in breast cancer are likely to affect the prognosis and outcome of treatment. In this study, we show a strong correlation between elevated levels of the Brn-3b POU transcription factor and high levels of HSP-27 protein in manipulated MCF-7 breast cancer cells as well as in human breast biopsies.

Activation of CDK4 gene expression in human breast cancer cells by the Brn-3b POU family transcription factor.

The Brn-3b POU family transcription factor has previously been shown to be over-expressed in human breast cancer and to enhance the growth rate and anchorage independent growth of human breast cancer cells, acting at least in part by inhibiting the expression of the BRCA-1 anti-oncogene. Here we have used gene arrays to identify several other targets for Brn-3b in human breast cancer cells, including cyclin-dependent kinase 4 (CDK4). In particular, we show that levels of CDK4 mRNA and protein correlate with the levels of Brn-3b in breast cancer cell lines manipulated to express different levels of Brn-3b and in human breast cancer biopsies and that Brn-3b can activate the CDK4 promoter.