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 provides strong support for the hypothesis that a small
number of cells, called cancer stem cells, are responsible for
fueling a tumor�
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, including estrogen, that can be
targeted with therapies. In the current study using both mice and
human breast cells, researchers found that BRCA1 regulated the
development of the estrogen-receptor-
estrogen-receptor-
unstable stem cells accumulate and then may develop into breast
cancers.
Researchers detected clusters of expanded stem cells in breast tissue
isolated from women carrying BRCA1 mutations, and found that women
with these expanded stem cells had a particularly high chance of
developing breast cancer.
�If larger studies confirm these findings, it could potentially lead
to a test to identify BRCA1 carriers at particularly high risk of
developing breast cancer. This might help them and their physicians
make a more informed decision about preventative measures such as
prophylactic mastectomy,&
BRCA1 mutations are the most common cause of hereditary breast
cancer, which account for approximately 10 percent of the 180,000
breast cancers diagnosed in the United States this year.
In addition to Wicha, study authors were U-M research investigator
Suling Liu; U-M research fellow Christophe Ginestier; Emmanuelle
Charafe-Jauffret, M.D., Ph.D., from the Centre de Recherche en
Cancerologie de Marseille in France; U-M research assistant Hailey
Foco; Celina Kleer, M.D., Harold A. Oberman Collegiate Professor of
Pathology and associate professor of pathology at U-M; Sofia
Merajver, M.D., Ph.D., professor of internal medicine at U-M; and
Gabriel Dontu, M.D., Ph.D., research assistant professor of internal
medicine at U-M.
The University of Michigan has filed for patents covering these and
related technologies, and, through its Office of Technology Transfer,
is currently looking for commercialization partners to help bring the
technology to market. Much of the work is being commercialized
through OncoMed, a University of Michigan startup company in which
Max Wicha and other U-M inventors hold a financial interest.
Reference: Proceedings of the NationalAcademy of Sciences, online
early edition, doi_10.1073_
Adapted from materials provided by University of Michigan Health
System.
http://www.topcance
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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