New insights into the role of estrogen receptor in mammary gland development may help scientists better understand the molecular origin of breast cancer.
About a decade ago, U.S. scientists at the National Institutes of Health (NIH) developed a standard estrogen receptor gene knock-out mouse model to study the estrogen receptor’s 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, doesn’t just affect the function of the receptor in all estrogen-responsive organs.
“It also creates an imbalance in the body’s circulating sex hormone levels, which could affect other physiological functions,” Khan adds. “An alternative model was clearly needed to study the intricacies of estrogen receptor’s 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 mammary glands.
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.
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 except mammary tissue, allowing scientists to study the receptor’s role in breast development and breast cancer.
Using this model, Khan’s team found that knocking out the gene only in mammary tissue resulted in abnormalities that compromised milk production in the nursing female. This suggests that estrogen expression is essential for normal duct development during puberty, pregnancy and lactation.
Khan and his coworkers reported the creation of this model and its potential implications in an online edition of the Proceedings of the National Academy of Sciences on Sept. 4, 2007, followed by the print issue Sept. 11, 2007.
The study directly refutes previous research, which suggests that estrogen receptor in epithelial cells was not essential to normal mammary gland development.