Navigation Links
UT Southwestern researchers discover a new driver of breast cancer
Date:11/7/2013

DALLAS Nov. 7, 2013 A team of researchers at UT Southwestern has found that as cholesterol is metabolized, a potent stimulant of breast cancer is created one that fuels estrogen-receptor positive breast cancers, and that may also defeat a common treatment strategy for those cancers.

The multidisciplinary team discovered that a cholesterol metabolite called 27-hydroxycholesterol, or 27HC, promotes tumor growth in estrogen-receptor positive breast cancers, which are the most common type of breast cancer. Estrogen-receptor positive breast cancer was previously believed to be stimulated primarily by the female sex hormone estrogen and it is commonly treated using endocrine-based medications that starve tumors of estrogen.

The discovery of 27HC as another driver of breast cancer may explain why endocrine-based therapy is often unsuccessful, providing a new target for therapy, the researchers say.

"This information can be used to develop new therapies that inhibit 27HC action or production, or increase its metabolism, in effect cutting the cancer off from a key growth stimulator," said senior author Dr. Philip Shaul, Professor and Vice Chair for Research in Pediatrics and a member of the Harold C. Simmons Comprehensive Cancer Center.

Implications of the research that appears in Cell Reports today are significant.

One million new cases of breast cancer are diagnosed each year, and about two-thirds of those are hormone receptor-positive, meaning they contain receptors for the hormones estrogen and/or progesterone, according to the American Cancer Society. Estrogen receptor-positive breast cancer is particularly prevalent following menopause.

Resistance to commonly used endocrine-based therapies occurs frequently, which led the researchers to recognize that important estrogen-independent processes must be driving the cancers' growth.

Dr. Shaul and his team first determined that 27HC stimulates the growth of breast cancer cells by hijacking growth-promoting mechanisms triggered by the estrogen receptor. The finding was first made in cultured cells, and then in mice. That prompted subsequent studies in postmenopausal women with estrogen receptor-positive breast cancer, who were compared to cancer-free control subjects.

Using specialized techniques developed by Dr. Jeffrey McDonald, Associate Professor of Molecular Genetics, the research team quantified levels of 27HC in tissue samples from UT Southwestern's Center for Breast Care. They found that in the breast cancer patients, 27HC content in normal breast tissue was markedly increased compared to that in cancer-free controls, and that tumor 27HC content was further elevated.

To explain why 27HC is so abundant in tumors, the team then turned to prior research in cholesterol metabolism by Dr. David Russell, Vice Provost and Dean of Basic Research at UT Southwestern, who previously discovered an enzyme called CYP7B1, which metabolizes 27HC. Querying a large database of tumor genes, they found that CYP7B1 is diminished in breast tumors compared with normal breast tissue. Further analysis revealed that there is a more than 7-fold poorer overall survival in women whose tumors display low CYP7B1, compared with women with high tumor CYP7B1.

Prior studies have shown that estrogen upregulates the 27HC metabolizing enzyme CYP7B1. Therefore, the commonly-used therapies that block estrogen synthesis or action may actually increase the abundance of this newly discovered promoter of breast cancer, the researchers also concluded.

"Measurements of tumor CYP7B1 or 27HC content could provide a potentially critical new means to personalize endocrine-based therapy for women with breast cancer," said Dr. Shaul. "Ultimately, the translation of these new findings to the clinical setting may also involve determinations of tumor CYP7B1 or 27HC abundance to serve as prognostic indicators."


'/>"/>

Contact: Alex Lyda
alex.lyda@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert  

Related medicine news :

1. Southwestern Ear, Nose, and Throat Hearing and Balance Center Welcomes Audiology Externs to Santa Fe
2. Dr. Jeffrey Kenkel Appointed as Education Director of Department of Plastic Surgery at UT Southwestern Medical Center
3. Southwestern Ear, Nose & Throat Associates Offers Guidelines On Hearing Loss, Lack of Sleep Affecting Back-to-School Health
4. 2 UT Southwestern scientists honored as rising stars in Texas research
5. Midlife fitness staves off chronic disease at end of life, UT Southwestern researchers report
6. UT Southwestern named the official health care team of the Dallas Stars
7. UT Southwestern investigators awarded $48.2 million in latest round of CPRIT grants
8. UT Southwestern study suggests new treatment target for deadly brain tumors
9. UT Southwestern study shows treating diabetes early, intensively is best strategy
10. Sanders-Brown researchers produce new research on little-understood brain disease
11. UCSF researchers offer solutions to looming health-care provider shortage
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
UT Southwestern researchers discover a new driver of breast cancer
(Date:10/13/2017)... ... October 13, 2017 , ... Dickinson ... offers insurance and financial preparation services, is providing an update on a charitable ... , Rock City Rescue is a locally recognized nonprofit that provides shelter and ...
(Date:10/13/2017)... ... October 13, 2017 , ... PurhealthRX , a leading Health ... technology. Applying the Purzorbℱprocess to full spectrum CBD oil will revolutionize the rapidly growing ... form that can be easily incorporated into liquid products, while reducing costs to end ...
(Date:10/13/2017)... , ... October 13, 2017 , ... The Visiting Nurse ... Market. Featuring a collection of specialty vendors and unique items from across the nation, ... quality-focused health and wellness services offered by the VNA. The boutique will be ...
(Date:10/13/2017)... VA (PRWEB) , ... October 13, 2017 , ... ... of DevOps and Agile Software Development, has been awarded a contract by the ... Blanket Purchase Agreement (BPA) aims to accelerate the enterprise use of Agile methodologies ...
(Date:10/12/2017)... Orleans, LA (PRWEB) , ... October 12, 2017 , ... ... centers in the U.S., announced today its plans to open a flagship location in ... will occupy the former Rooms To Go store next to Office Depot in the ...
Breaking Medicine News(10 mins):
(Date:10/11/2017)...  True Health, a leader in integrated diagnostics ... National Breast Cancer Awareness month to educate doctors ... Research recently published in ... than 10 million American women are at significant ... BRCA2 and have not had testing. These mutations can ...
(Date:10/7/2017)... 6, 2017   Provista, a proven leader ... billion in purchasing power, today announced a new resource ... The Newsroom is the online home for case ... expert bios, news releases, slideshows and events. ... wealth of resources at their fingertips, viewers can also ...
(Date:10/4/2017)... Mass. , Oct. 4, 2017 ... of single-use, self-contained, illuminating medical devices, today announced ... National Health Surveillance Agency (or AgĂȘncia Nacional de ... The first single-use, cordless surgical retractor with integrated ... provides optimal access, illumination and exposure of a ...
Breaking Medicine Technology: