PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

UT Southwestern researchers discover a new driver of breast cancer

2013-11-07
(Press-News.org) Contact information: Alex Lyda
alex.lyda@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
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."



INFORMATION:

Other UT Southwestern researchers on the team included Dr. Qian Wu, Dr. Tomonori Ishikawa, Dr. Rosa Sirianni, Dr. Hao Tang, Dr. Jeffrey G. McDonald, Dr. Ivan S. Yuhanna, Dr. Bonne Thompson, Dr. Luc Girard, Dr. Chieko Mineo, Dr. Rolf Brekken, Dr. Michihisa Umetani, and Dr. Yang Xie.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including five who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 90,000 hospitalized patients and oversee more than 1.9 million outpatient visits a year.

This news release is available on our home page at http://www.utsouthwestern.edu/home/news/index.html

To automatically receive news releases from UT Southwestern via email, subscribe at http://www.utsouthwestern.edu/receivenews



ELSE PRESS RELEASES FROM THIS DATE:

'Freakish' asteroid discovered, resembles rotating lawn sprinkler

2013-11-07
'Freakish' asteroid discovered, resembles rotating lawn sprinkler Astronomers have discovered a "weird and freakish object" resembling a rotating lawn sprinkler in the asteroid belt between Mars and Jupiter. The find, reported online in the ...

Horrors of war harden group bonds

2013-11-07
Horrors of war harden group bonds War is hell, and according to new research, experiencing the horrors of war can cause people to have a greater affinity for members of their own group, particularly if individuals are exposed to war during key periods of their ...

UCSF scientist asks, did inefficient cellular machinery evolve to fight viruses and jumping genes?

2013-11-07
UCSF scientist asks, did inefficient cellular machinery evolve to fight viruses and jumping genes? It might seem obvious that humans are elegant and sophisticated beings in comparison to lowly bacteria, but when it comes to genes, a UC San ...

Changes to fisheries legislation have removed habitat protection for most fish species in Canada

2013-11-07
Changes to fisheries legislation have removed habitat protection for most fish species in Canada University of Calgary and Dalhousie University fisheries biologists say federal Fisheries Act revisions were unscientific Federal government changes to Canada's ...

Tree nut consumption associated with reduced risk of pancreatic cancer in women

2013-11-07
Tree nut consumption associated with reduced risk of pancreatic cancer in women First prospective study to date on nut consumption and pancreatic cancer in the Bristish Journal of Cancer Davis, CA, November 7, 2013 – In a large prospective study published online ...

Getting to grips with seizure prediction

2013-11-07
Getting to grips with seizure prediction A device that could predict when a person with epilepsy might next have a seizure is one step closer to reality thanks to the development of software by researchers in the USA. Details are to be published in a forthcoming issue of the ...

Programmed nanoparticles organize themselves into highly complex nanostructures

2013-11-07
Programmed nanoparticles organize themselves into highly complex nanostructures New principle for the self-assembly of patterned nanoparticles published in NATURE may have important implications for nanotechnology and future technologies Animal ...

Hartz IV reform did not reduce unemployment in Germany

2013-11-07
Hartz IV reform did not reduce unemployment in Germany Impact of the Hartz IV reform on curbing unemployment in Germany proved to be exceptionally low The Hartz IV reform of the German labor market has been one of the most controversial ...

New study shows trustworthy people are perceived to look similar to ourselves

2013-11-07
New study shows trustworthy people are perceived to look similar to ourselves When a person is deemed trustworthy, we perceive that person's face to be more similar to our own, according to a new study published in Psychological Science. A team of scientists ...

Why stem cells need to stick with their friends

2013-11-07
Why stem cells need to stick with their friends Scientists at University of Copenhagen and University of Edinburgh have identified a core set of functionally relevant factors which regulates embryonic stem cells' ability for self-renewal. A key aspect ...

LAST 30 PRESS RELEASES:

Robotic space rovers keep getting stuck. UW engineers have figured out why

New research shows how immigration status can become a death sentence during public health crisis

University of Toronto Engineering researchers develop safer alternative non-stick coating

Good vibrations: Scientists use imaging technology to visualize heat

More ecological diversity means better nutritional resources in Fiji’s agroforests

New global study shows freshwater is disappearing at alarming rates

Scientists create an artificial cell capable of navigating its environment using chemistry alone

A little salt is good for battery health

Deep-sea fish confirmed as a significant source of ocean carbonate

How to keep kids with eating disorders home after hospital stay? Therapy

Sex differences affect efficacy of opioid overdose treatment

Aligning AI with Human Values and Well-Being

Engineering the next generation of experimental physics

The scuba diving industry is funding marine ecosystem conservation and employing locals

BATMAN brings TCR therapy out of the shadows

Surrogates more likely to be diagnosed with mental illness, study finds

Columbia Engineering researchers turn dairy byproduct into tissue repair gel

Global estimates of lives and life-years saved by COVID-19 vaccination during 2020-2024

Potential trade-offs of proposed cuts to the NIH

New research simulates cancer cell behavior

COVID, over 2.5 million deaths prevented worldwide thanks to vaccines. One life saved for every 5,400 doses administered

Scuba diving generates up to $20 billion annually

Scientists advance efforts to create ‘virtual cell lab’ as testing ground for future research with live cells

How DNA packaging controls the “genome’s guardian”

Simplified models, deeper insights: Coarse-grained models unlock new potential for ionic liquid simulations

Gorillas’ personal circumstances shape their aggression towards groupmates

Which signalling pathways in the cell lead to possible therapies for Parkinson's disease

Identifying landslide threats using hydrological predictors

First graders who use more educational media spend more time reading

Exploring the meaning in life through phenomenology and philosophy

[Press-News.org] UT Southwestern researchers discover a new driver of breast cancer