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. 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.
Samady
Laila
L
Medical Molecular Biology Unit, Institute of Child Health, University College London, London, United Kingdom. L.Samady@ich.ucl.ac.uk
Faulkes
David J
DJ
Budhram-Mahadeo
Vishwanie
V
Ndisang
Daniel
D
Potter
Eyck
E
Brabant
Georg
G
Latchman
David S
DS
D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002448:Cell Adhesion; D051180:Desmoplakins; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D050820:Transcription Factor Brn-3B / Q000502:physiology*; D014407:Tumor Cells, Cultured; D051185:gamma Catenin / Q000096:biosynthesis*
D051180:Desmoplakins; C495292:JUP protein, human; C494190:POU4F2 protein, human; D050820:Transcription Factor Brn-3B; D051185:gamma Catenin