Navigation Links
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 except mammary tissue, allowing scientists to study the receptors role in breast development and breast cancer.

Using this model, Khans 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 report the creation of this model and its potential implications in an early 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.

Mammary tissue is made up of two cell typesstromal cells, which give the tissue structure, and epithelial cells, which make up the lining of the mammary gland and become cancerous in the majority of breast cancers.

Unlike other organs in the body, the mammary glands develop after birth in response to increases in circulating hormones. This triggers growth of a network of branched ducts throughout the breast tissue that do not change again until a woman becomes pregnant.

Even though the relationship between the estrogen receptor and breast cancer is well established, we still know very little about the receptors mechanism of action, explains Khan, corresponding author of the study. Unless we study those mechanisms more closely, improved strategies for breast cancer treatments will not be possible.

Premenopausal women with breast cancer are currently given five years of tamoxifen, a drug that blocks the estrogen receptor action in cancer cells, to prevent recurrence. Studies have shown that the drug reduces recurrence in 40 percent of the women who take it, but Khan says many women eventually develop resistance to the drug.

Using this unique mouse model, UC researchers are currently collaborating with scientists at Dana Farber Cancer Institute/Harvard Medical School to understand the relationship between estrogen-signaling and oncogene-mediated breast cancer development. Future findings from these studies could help scientists better understand the molecular origin of breast cancer and develop new drugs to more effectively treat it.


'/>"/>

Contact: Amanda Harper
amanda.harper@uc.edu
513-558-4657
University of Cincinnati
Source:Eurekalert

Related medicine news :

1. Down syndrome simulated in animal model after successful chromosome transplantation
2. Novel computer model for breast cancer
3. MRI, To Detect Remodeling Of Heart and Help Preserve Function
4. Synthetic protein found to relieve arthritis symptoms in animal model
5. Researchers Develop Mouse Model Of Brain Tumor
6. New Model for understanding Tumor Metastasis
7. Mathematical Model Can Now Help Predict Asthma Risk
8. Model Kate Moss - Re-Birth After Humiliation
9. Heart transplanted infants better model for developing AIDS treatment
10. Mice model to study bacterial therapeutic pathway
11. Womens Self-Esteem Not Lowered By Seeing Ultra Thin Models
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... ... Austin residents seeking Mohs surgery services, can now turn to Dr. Jessica Scruggs ... for medical and surgical dermatology. , Dr. Dorsey brings specialization to include Mohs surgery, ... Micrographic Surgery completed by Dr. Dorsey was under the direction of Glenn Goldstein, MD, ...
(Date:6/25/2016)... Oklahoma City, Oklahoma (PRWEB) , ... June 25, ... ... to helping both athletes and non-athletes recover from injury. Recently, he has implemented ... for the Oklahoma City area —Johnson is one of the first doctors to ...
(Date:6/24/2016)... ... , ... June 19, 2016 is World Sickle Cell Observance Day. In an ... of holistic treatments, Serenity Recovery Center of Marne, Michigan, has issued a ... Cell Disease (SCD) is a disorder of the red blood cells, which can cause ...
(Date:6/24/2016)... ... June 24, 2016 , ... Comfort Keepers® of San ... Society and the Road To Recovery® program to drive cancer patients to and from ... adults to ensure the highest quality of life and ongoing independence. Getting to ...
(Date:6/24/2016)... Vegas, Nevada (PRWEB) , ... June 24, 2016 ... ... Las Vegas client, The Grove Investment Group (TGIG), has initiated cultivation and processing ... Grove, in Las Vegas and Pahrump, Nevada. , Puradigm is the manufacturer of ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)...   Pulmatrix, Inc ., (NASDAQ: PULM ... announced today that it was added to the Russell ... comprehensive set of U.S. and global equity indexes on ... milestone for Pulmatrix," said Chief Executive Officer Robert ... progress in developing drugs for crucial unmet medical needs, ...
(Date:6/23/2016)... BEVERLY HILLS, Calif. , June 23, 2016 ... faced the many challenges of the current process. Many of ... option because of the technical difficulties and high laboratory costs ... would have to offer it at such a high cost ... to afford it. Dr. Parsa Zadeh , ...
(Date:6/23/2016)... 2016 Capricor Therapeutics, Inc. ... biotechnology company focused on the discovery, development and ... enrollment in its ongoing randomized HOPE-Duchenne clinical trial ... of its 24-patient target. Capricor expects the trial ... of 2016, and to report top line data ...
Breaking Medicine Technology: