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BRCA1 mutation linked to breast cancer stem cells
Date:1/31/2008

ANN ARBOR, Mich. A new study may explain why women with a mutation in the BRCA1 gene face up to an 85 percent lifetime risk of breast cancer.

Researchers from the University of Michigan Comprehensive Cancer Center found that BRCA1 plays a role in regulating breast stem cells, the small number of cells that might develop into cancers.

The study, in mice and in human breast cancer cells, found that BRCA1 is involved in the stem cells differentiating into other breast tissue cells. When BRCA1 is missing, the stem cells accumulate unregulated and develop into cancer.

Our data suggest that an important reason women with BRCA1 mutations get breast cancer is that BRCA1 is directly involved in the regulation of normal breast stem cells. In these women, loss of BRCA1 function results in the proliferation of breast stem cells. Since we believe that breast cancer may originate in these cells, this explains why these women have such a high incidence of breast cancer, said senior study author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center.

The study, published online this week in the Proceedings of the National Academy of Sciences, provides strong support for the hypothesis that a small number of cells, called cancer stem cells, are responsible for fueling a tumors growth. Wichas lab was part of the team that first identified stem cells in human breast cancer in 2003.

BRCA1 is one of two genes, that when mutated confers a high risk of breast and ovarian cancer. Previous research has shown that BRCA1 is involved in DNA repair, but it has been unclear why women with this gene mutation have such a high risk of breast cancer, up to 85 percent lifetime risk compared to 16 percent in the general population.

The cancers which develop in these women are generally a more aggressive form called triple negative type, because they do not express hormones or proteins,
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Contact: Nicole Fawcett
nfawcett@umich.edu
734-764-2220
University of Michigan Health System
Source:Eurekalert

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