The Brn-3b POU family transcription factor represses plakoglobin gene expression in human breast cancer cells.
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| 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 (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.
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| Authors | Laila Samady, David J Faulkes, Vishwanie Budhram-Mahadeo, Daniel Ndisang, Eyck Potter, Georg Brabant, David S Latchman |
| Journal | International journal of cancer (Int J Cancer) Vol. 118 Issue 4 Pg. 869-78 (Feb 15 2006) ISSN: 0020-7136 [Print] United States |
| PMID | 16152597 (Publication Type: Journal Article) |
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