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New findings may improve treatment of inherited breast cancer
Date:10/9/2008

Scientists have identified some of the elusive downstream molecules that play a critical role in the development and progression of familial breast cancer. The research, published by Cell Press in the October 10th issue of the journal Molecular Cell, also identifies a compound found in grapes and red wine as an excellent candidate for treatment of some forms of breast cancer.

About 8% of breast cancer cases are caused by mutations in tumor suppressor genes, such as breast cancer associated gene-1 (BRCA1). BRCA1 is the most frequently mutated tumor suppressor gene found in inherited breast cancers and BRCA1 mutation carriers have a 50-80% risk of developing breast cancer by age 70. "Although work with animal models of BRCA1 mutation has provided some insight into the many biological processes linked with BRCA1, very little is known about the downstream mediators of BRCA1 function in tumor suppression," says lead study author Dr. Chu-Xia Deng from the Genetics of Development and Diseases Branch at the National Institutes of Health.

Dr. Deng and colleagues were interested in investigating the relationship among BRCA1, SIRT1 and Survivin. SIRT1 is a protein and histone deacetylase involved in numerous critical cell processes including metabolism, DNA repair and programmed cell death, known as apoptosis. Although SIRT1 has been implicated in tumorigenesis, no concrete role in cancer initiation or progression has been identified. Survivin is an apoptosis inhibitor that is dramatically elevated in many types of tumors. Research has suggested that Survivin may serve to maintain the tumor and promote growth.

The researchers found that BRCA1 functioned as a tumor suppressor by maintaining SIRT1 expression, which in turn inhibited Survivin expression. When BRCA1 was not functioning properly, SIRT levels decreased and Survivin levels increased, allowing BRCA1-deficient cells to overcome apoptosis and undergo malignant transformation.


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Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

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