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New 'knock-out' gene model provides molecular clues to breast cancer
Date:9/5/2007

New insights into the role of estrogen receptor in mammary gland development may help scientists better understand the molecular origin of breast cancer, according to new research from the University of Cincinnati (UC).

About a decade ago, U.S. scientists at the National Institutes of Health (NIH) developed a standard estrogen receptor (ER) gene knock-out mouse model to study the estrogen receptors role in human diseases.

Unfortunately, because these mice lacked mammary glands as a consequence of genetic manipulation, using this model to study the relationship between the estrogen receptor and breast cancer proved ineffective, explains Sohaib Khan, PhD, professor of cell and cancer biology at UC.

Knocking out the estrogen receptor gene for the entire genome, as the NIH scientists did, doesnt just affect the function of the receptor in all estrogen-responsive organs. It also creates an imbalance in the bodys circulating sex hormone levels, which could affect other physiological functions, Khan adds. An alternative model was clearly needed to study the intricacies of estrogen receptors involvement in this disease.

Estrogen receptor is a cellular protein that binds with the hormone estrogen and facilitates action in different parts of the body, including the mammary gland. Research has shown that about 70 percent of breast cancer patients have estrogen receptor-positive breast cancer, meaning their tumors will have some beneficial response to anti-estrogen drugs like tamoxifen (ta-MOX-ee-fen, marketed as Nolvodex).

After two years of work, Khan says his team has developed a knock-out mouse model that will allow scientists to study the role of estrogen receptor in specific organs (for example, mammary glands) without affecting estrogen-signaling throughout the rest of its body.

Khan used what is called a conditional knock-out technique to develop a new mouse model that retains estrogen receptor in all tissues
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Contact: Amanda Harper
amanda.harper@uc.edu
513-558-4657
University of Cincinnati
Source:Eurekalert

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