Abstract
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. Here, we show that Brn‐3b regulates plakoglobin (γ‐catenin), a member of the catenin family involved in cell‐cell adhesion and signal transduction. Brn‐3b expression inversely correlates with plakoglobin expression at both mRNA and protein levels in breast cancer cell lines and human breast biopsies. In contrast, no significant correlation was observed between Brn‐3b expression and β‐catenin, or between Brn‐3b expression and E‐cadherin expression. Brn‐3b represses the plakoglobin promoter via a Brn‐3 consensus binding site contained within the region −965 to −593 relative to the transcriptional start site. Both repression of the promoter and binding of Brn‐3b are lost when this site is mutated. To our knowledge, this is the first time that a Brn‐3b POU family transcription factor has been shown to regulate a member of the catenin family, which provides insight into the molecular mechanisms by which Brn‐3b expression may favour breast cancer progression and tumor invasion. © 2005 Wiley‐Liss, Inc.