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

High cholesterol fuels the growth and spread of breast cancer

2013-11-29
(Press-News.org) Contact information: Sarah Avery
sarah.avery@duke.edu
919-660-1306
Duke University Medical Center
High cholesterol fuels the growth and spread of breast cancer

DURHAM, N.C. – A byproduct of cholesterol functions like the hormone estrogen to fuel the growth and spread of the most common types of breast cancers, researchers at the Duke Cancer Institute report.

The researchers also found that anti-cholesterol drugs such as statins appear to diminish the effect of this estrogen-like molecule.

Published in the Nov. 29, 2013, edition of the journal Science, the findings are early, using mouse models and tumor cells. But the research for the first time explains the link between high cholesterol and breast cancer, especially in post-menopausal women, and suggests that dietary changes or therapies to reduce cholesterol may also offer a simple, accessible way to reduce breast cancer risk.

"A lot of studies have shown a connection between obesity and breast cancer, and specifically that elevated cholesterol is associated with breast cancer risk, but no mechanism has been identified," said senior author Donald McDonnell, Ph.D., chair of the Department of Pharmacology and Cancer Biology at Duke. "What we have now found is a molecule – not cholesterol itself, but an abundant metabolite of cholesterol – called 27HC that mimics the hormone estrogen and can independently drive the growth of breast cancer."

The hormone estrogen feeds an estimated 75 percent of all breast cancers. In a key earlier finding from McDonnell's lab, researchers determined that 27-hydroxycholesterol – or 27HC – behaved similarly to estrogen in animals.

For their current work, the researchers set out to determine whether this estrogen activity was sufficient on its own to promote breast cancer growth and metastasis, and whether controlling it would have a converse effect.

Using mouse models that are highly predictive of what occurs in humans, McDonnell and colleagues demonstrated the direct involvement of 27HC in breast tumor growth, as well as the aggressiveness of the cancer to spread to other organs. They also noted that the activity of this cholesterol metabolite was inhibited when the animals were treated with antiestrogens or when supplementation of 27HC was stopped.

The studies were substantiated using human breast cancer tissue. An additional finding in the human tissue showed a direct correlation between the aggressiveness of the tumor and an abundance of the enzyme that makes the 27HC molecule. They also noted that 27HC could be made in other places in the body and transported to the tumor.

"The worse the tumors, the more they have of the enzyme," said lead author Erik Nelson, Ph.D., a post-doctoral associate at Duke. Nelson said gene expression studies revealed a potential association between 27HC exposure and the development of resistance to the antiestrogen tamoxifen. Their data also highlights how increased 27HC may reduce the effectiveness of aromatase inhibitors, which are among the most commonly used breast cancer therapeutics.

"This is a very significant finding," McDonnell said. "Human breast tumors, because they express this enzyme to make 27HC, are making an estrogen-like molecule that can promote the growth of the tumor. In essence, the tumors have developed a mechanism to use a different source of fuel."

McDonnell said the findings suggest there may be a simple way to reduce the risk of breast cancer by keeping cholesterol in check, either with statins or a healthy diet. Additionally, for women who have breast cancer and high cholesterol, taking statins may delay or prevent resistance to endocrine therapies such as tamoxifen or aromatase inhibitors.

The next steps for research include clinical studies to verify those potential outcomes, as well as studies to determine if 27HC plays a role in other cancers, McDonnell said.



INFORMATION:

In addition to McDonnell and Nelson, study authors include Suzanne E. Wardell, Jeff S. Jasper, Sunghee Park, Sunil Suchindran, Matthew K. Howe, Nicole J. Carver, Ruchita V. Pillai, Patrick M. Sullivan, Varun Sondhi, Michihisa Umetani and Joseph Geradts.

The National Institutes of Health (K99CA172357) (R37DK048807) and the Department of Defense funded the study.



ELSE PRESS RELEASES FROM THIS DATE:

Scripps Research Institute scientists achieve most detailed picture ever of key part of hepatitis C

2013-11-29
Scripps Research Institute scientists achieve most detailed picture ever of key part of hepatitis C LA JOLLA, CA—November 28, 2013—Scientists at The Scripps Research Institute (TSRI) have determined the most detailed picture yet of a crucial part of the hepatitis ...

Researchers find a missing component in effort to create primitive, synthetic cells

2013-11-29
Researchers find a missing component in effort to create primitive, synthetic cells A team of Massachusetts General Hospital (MGH) investigators working to create "protocells" – primitive synthetic cells consisting of a nucleic acid strand encased within ...

Fruit flies with better sex lives live longer

2013-11-29
Fruit flies with better sex lives live longer Can sexual frustration be bad for your health? Male fruit flies that expected sex -- and didn't get it -- experienced serious health consequences and aged faster ANN ARBOR, Mich. — Sex may in fact be ...

Quantitative approaches provide new perspective on development of antibiotic resistance

2013-11-29
Quantitative approaches provide new perspective on development of antibiotic resistance Using quantitative models of bacterial growth, a team of UC San Diego biophysicists has discovered the bizarre way by which antibiotic resistance allows bacteria ...

Memories are 'geotagged' with spatial information, Penn researchers say

2013-11-29
Memories are 'geotagged' with spatial information, Penn researchers say Using a video game in which people navigate through a virtual town delivering objects to specific locations, a team of neuroscientists from the University of Pennsylvania and Freiburg University ...

Stanford study suggests why, in some species, mere presence of males shortens females' lifespan

2013-11-29
Stanford study suggests why, in some species, mere presence of males shortens females' lifespan STANFORD, Calif. — Researchers at the Stanford University School of Medicine have discovered that males of the laboratory roundworm secrete signaling molecules ...

Bone grafting improvements with the help of sea coral

2013-11-29
Bone grafting improvements with the help of sea coral Sea coral could soon be used more extensively in bone grafting procedures thanks to new research that has refined the material's properties and made it more compatible with natural bone. By partially converting ...

Follow your gut down the aisle, new study says

2013-11-29
Follow your gut down the aisle, new study says Newlyweds know on subconscious level whether marriage will be unhappy TALLAHASSEE, Fla. — Although newlyweds may not be completely aware of it, they may know whether their march down the aisle will result in wedded bliss or an ...

Methylation signaling controls angiogenesis and cancer growth

2013-11-29
Methylation signaling controls angiogenesis and cancer growth (Boston) – A study led by researchers at Boston University School of Medicine (BUSM) demonstrates a new mechanism involving a signaling protein and its receptor that may block the formation ...

Iron-based process promises greener, cheaper and safer drug and perfume production

2013-11-29
Iron-based process promises greener, cheaper and safer drug and perfume production TORONTO, ON – University of Toronto researchers have developed a series of techniques to create a variety of very active iron-based catalysts necessary to produce the alcohols and ...

LAST 30 PRESS RELEASES:

New post-hoc analysis shows patients whose clinicians had access to GeneSight results for depression treatment are more likely to feel better sooner

First transplant in pigs of modified porcine kidneys with human renal organoids

Reinforcement learning and blockchain: new strategies to secure the Internet of Medical Things

Autograph: A higher-accuracy and faster framework for compute-intensive programs

Expansion microscopy helps chart the planktonic universe

Small bat hunts like lions – only better

As Medicaid work requirements loom, U-M study finds links between coverage, better health and higher employment

Manifestations of structural racism and inequities in cardiovascular health across US neighborhoods

Prescribing trends of glucagon-like peptide 1 receptor agonists for type 2 diabetes or obesity

Continuous glucose monitoring frequency and glycemic control in people with type 2 diabetes

Bimodal tactile tomography with bayesian sequential palpation for intracavitary microstructure profiling and segmentation

IEEE study reviews novel photonics breakthroughs of 2024

New method for intentional control of bionic prostheses

Obesity treatment risks becoming a ‘two-tier system’, researchers warn

Researchers discuss gaps, obstacles and solutions for contraception

Disrupted connectivity of the brainstem ascending reticular activating system nuclei-left parahippocampal gyrus could reveal mechanisms of delirium following basal ganglia intracerebral hemorrhage

Federated metadata-constrained iRadonMAP framework with mutual learning for all-in-one computed tomography imaging

‘Frazzled’ fruit flies help unravel how neural circuits stay wired

Improving care for life-threatening blood clots

Yonsei University develops a new era of high-voltage solid-state batteries

Underweight and unbalanced: Gut microbial diversity in underweight Japanese women

Astringent, sharper mind: Flavanols trigger brain activity for memory and stress response

New editorial urges clinicians to address sex-based disparities in sepsis treatment

Researchers at MIT develop new nanoparticles that stimulate the immune system to attack ovarian tumors

Opening the door to a vaccine for multiple childhood infections

New clue to ALS and FTD: Faulty protein disrupts brain’s ‘brake’ system

Detailed map of US air-conditioning usage shows who can beat the heat — and who can’t

An electronic fiber for stretchable sensing

New image captures spooky bat signal in the sky

Cobalt single atom-phosphate functionalized reduced graphene oxide/perylenetetracarboxylic acid nanosheet heterojunctions for efficiently photocatalytic H2O2 production

[Press-News.org] High cholesterol fuels the growth and spread of breast cancer