Regulation of BRCA-1 Gene Expression and Mammary Tumorigenesis by the Brn-3b POU Family Transcription Factor
Abstract
The Brn-3b POU family transcription factor is over-expressed in breast cancer cells compared to normal mammary cells. Moreover, the levels of Brn-3b in individual tumors show an inverse correlation with the expression levels of the BRCA-1 anti-oncoprotein. In this project, we have demonstrated that Brn-3b represses the activity of a 500 base pair fragment of the BRCA-l gene, which contains two distinct BRCA-1 promoters (alpha and beta). Moreover, we have shown using further constructs that the alpha and beta promoters are independently repressed by Brn-3b. We have also prepared human breast cancer MCF-7 cell lines, which have been stably transfected with vectors expressing the sense or anti-sense strand of Brn-3b. These cell lines exhibit respectively increased or decreased Brn-3b levels compared to cells transfected with empty expression vector. The cells with enhanced Brn-3b levels show enhanced growth rates and saturation density compared to the control cells, whilst the cells with reduced Brn-3b levels show reduced growth rate and saturation density. These results thus establish, for the first time, the ability of Brn-3b to modulate the growth of breast cancer cells and its ability to activate the BRCA-1 alpha and beta gene promoters.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2000
- Accession Number
- ADA389424
Entities
People
- David S. Latchman
Organizations
- University College London