Navigation Links
UT Southwestern researchers discover a new driver of breast cancer

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
UT Southwestern Medical Center

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:
Related Image:
UT Southwestern researchers discover a new driver of breast cancer
(Date:11/30/2015)... ... November 30, 2015 , ... Olympic Gold Medalists and Celebrity ... brands across various categories through traditional and social media marketing campaigns and other ... of Gold Medal Moms who can connect with today’s most important consumer: mothers. ...
(Date:11/30/2015)... ... December 01, 2015 , ... The ... a 2015-2016 inductee into its VIP Woman of the Year Circle. She is ... leading networking organization exclusively for professional women, boasting 850,000 members and over 200 ...
(Date:11/30/2015)... , ... November 30, 2015 , ... ... (Meso Foundation) released information for caregivers and held two webinars on topics of ... on demand free of charge at . , With a loved ...
(Date:11/30/2015)... ... November 30, 2015 , ... MOSI recently added two state-of-the-art augmented reality (AR) ... the Jurassic to their collection of interactive exhibits within the Kids In Charge! building. ... allow guests to get closer than ever to a range of animals as they ...
(Date:11/30/2015)... VA (PRWEB) , ... November 30, 2015 , ... ... mesothelioma-affected community across the United States to access life-saving information provided ... Malignant Mesothelioma will consist of three individual conferences in three major cities: ...
Breaking Medicine News(10 mins):
(Date:11/30/2015)... , Nov. 30, 2015  QT Vascular Ltd., ... and together with its subsidiaries, TriReme Medical LLC and ... company engaged in the design, assembly and distribution of ... vascular disease, is pleased to announce that a three-judge ... Court of Appeals for the Federal Circuit ("Federal Circuit") ...
(Date:11/30/2015)... 2015   Royal Philips  (NYSE: PHG ... Radiology Solutions, a fully integrated, consultative approach to ... data-driven practice management approaches that combine imaging systems, ... improve care delivery and reduce costs. Making its ... North America Annual Meeting (RSNA) in ...
(Date:11/30/2015)... -- Nautilus Medical Inc. today announced worldwide availability of ... ). The release of MatrixRay to the entire medical ... North America) in Chicago - ... --> --> MatrixRay is the ... studies worldwide via a peer-to-peer exchange network of physicians ...
Breaking Medicine Technology: