By comparing mutated and normal forms of BRCA-2 in mouse cells, Sook Shin found that the normal BRCA-2 enhanced the androgen receptors' transcriptional activity (copying DNA into RNA, ultimately producing gene products) by binding with the receptor. The binding, however, could only happen with the help of GRIP1 and enhanced activity by 10-fold. Furthermore BRCA2 and GRIP1 cooperate with histone acetyl transferase enzymes required for remodeling chromatin, the material in chromosomes, providing more evidence of BRCA-2's role in DNA repair and possible tumor suppression. The mutant form of BRCA-2 could not enhance androgen receptor activity.
The scientists' work will take several years before there is any sign of a new treatment for cancer. But since people who have the mutated form of BRCA-1 or 2 face a much higher chance of getting cancer than normal, knowing how these genes work should eventually prove invaluable in reducing cases of cancer.
Verma's team now is looking at what other genes are turned on by this interaction of BRCA-2, GRIP1 and male sex hormones, and what are the specific targets in the cell of the breast cancer genes.
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Contact: Andrew Porterfield
porterfield@salk.edu
858-453-4100 x1340
Salk Institute
27-Jun-2003