The study, published in the June 10 Proceedings of the National Academy of Sciences, provides details on how the normal form of the gene may work, and how mutant forms of BRCA-2 may malfunction and therefore likely contribute to the development of breast cancer. It also gives greater insight into the causes of male breast cancer. BRCA-2 is one of two genes (the other is BRCA-1) linked to at least 10 percent of all breast cancers; the mutant form appears in nearly all male breast cancers.
Sook Shin, a postdoctoral fellow at the Salk, and Inder Verma, a Salk professor of genetics, found that the normal form of BRCA-2 enhanced the activity of androgen receptors that bind to androgens, which are male sex hormones like testosterone. Androgens exhibit antiproliferative activity in addition to their actions in developing male sex characteristics. Women also produce androgens, but have different levels in their bodies; the hormones play a role in female and male cancers.
In its mutated form, however, BRCA-2 could not enhance the androgen receptor's activity and thus may allow cancer cells to proliferate, the scientists discovered. Interestingly, for BRCA2 to function, it needs to synergize with co-activators located on the cell nucleus named GRIP1, a protein previously identified by Salk scientists working on nuclear hormone receptors in Salk Professor Ron Evans' laboratory.
"We think that BRCA-2 may be involved in DNA repair, or synthesis of new gene products, but haven't had enough detail on how this gene functions," said Verma. "This study shows how BRCA-2 helps androgen receptors do a better job of perhaps suppressing tumors, and may help us arrive at new targets for treating or preventing breast canc
'"/>
Contact: Andrew Porterfield
porterfield@salk.edu
858-453-4100 x1340
Salk Institute
27-Jun-2003