Breast Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Breast Cancer, including details on symptoms, genetics, screening, treatment, information. | ||||||||
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The Brn-3b POU family transcription factor represses plakoglobin gene expression in human breast cancer cells.Samady L, Faulkes DJ, Budhram-Mahadeo V, Ndisang D, Potter E, Brabant G, Latchman DS Medical Molecular Biology Unit, Institute of Child Health, University College London, London, United Kingdom. L.Samady@ich.ucl.ac.uk 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 (gamma-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 beta-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. Published 1 February 2006 in Int J Cancer, 118(4): 869-78.
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