Regulation of BRCA-1 Gene Expression and Mammary Tumorigenesis by the Brn-3b POU Family Transcription Factor
Final rept. 1 Dec 1999-30 Nov 2002
UNIVERSITY COLL LONDON (UNITED KINGDOM)
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The Brn-3b POU family transcription factor is over-expressed in breast cancer cells compared to normal mammary cells. In this project, we have stably transfected the human breast cancer cell line MCF-7 with vectors expressing the sense or anti-sense strand of Brn-3b so as to isolate cell lines with respectively enhanced or reduced Brn-3b levels. The cell lines with enhanced Brn-3b levels show enhanced growth rate, saturation density, cell division, anchorage independence in vitro and enhanced ability to form tumors in vivo. In contrast, the cell lines with reduced Brn-3b show reductions in all those growth parameters. In addition, the cell lines with altered Brn-3b levels show altered expression of genes such as BRCA-l and the oestrogen receptor whose expression is known to be modulated in breast cancer. These findings thus establish Brn-3b as a key factor regulating gene expression and growth of human breast cancer cells.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research