Featured Research

from universities, journals, and other organizations

Molecular link between metabolism and breast cancer

Date:
February 6, 2013
Source:
National Cancer Institute (NCI) at NIH
Summary:
A protein associated with conditions of metabolic imbalance, such as diabetes and obesity, may play a role in the development of aggressive forms of breast cancer, according to new findings.

Breast cancer cells in a normal gland stained as small brown ovoids. Also shown is an inhibitory molecule that has been digitized to indicate the level of CtBP expression, with red showing high levels, yellow showing low levels, and white showing no expression.
Credit: Image courtesy of National Cancer Institute (NCI) at NIH

A protein associated with conditions of metabolic imbalance, such as diabetes and obesity, may play a role in the development of aggressive forms of breast cancer, according to new findings by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, and their colleagues. Metabolic imbalance is often caused by elevated carbohydrate intake, which can lead to over-activating a molecule called C-terminal binding protein (CtBP). This over-activation, in turn, can increase the risk of breast cancer. Results of their work appeared in Nature Communications, Feb. 5, 2013.

Related Articles


"Modifying diet and maintaining a healthy diet, combined with developing pharmacological ways of lessening CtBP activity, may one day lead to a way to break the link between cancer and obesity," said Kevin Gardner, M.D., Ph.D., head of NCI's Transcription Regulation Section, Genetics Branch.

It has been known, primarily through population based studies, that there is a strong link between obesity and cancer. But the mechanism behind this link has been uncertain. A previous study conceived and carried out in Gardner's laboratory found that CtBP repressed expression of a gene associated with breast cancer (BRCA1) at an early age by sensing when the cell was in a high metabolic state that, in turn, led to processing large amounts of carbohydrates in the body.

This early study suggested that obesity and weight gain may contribute to breast cancer by decreasing the level of the BRCA1 tumor suppressor gene expression in response to high carbohydrate intake. This explains, in part, why women who have hereditary mutations of BRCA1 also experience an increased risk of breast cancer if they gain weight.

Gardner's new study expands upon his past work. He analyzed prior gene expression studies to determine if gene pathways, repressed by CtBP, were diminished in breast cancer patients who suffered from more aggressive clinical outcomes. Gardner's team began first with the human breast cancer cells in the laboratory. They measured the association of CtBP and the genes it bound to in order to regulate expression. The researchers combined this approach with genome sequencing to confirm how, and where, CtBP bound to genes associated with breast cancer. Next, they integrated analyses with gene expression studies in cells in which they observed decreased the levels of CtBP by RNA interference (a process that inhibits gene expression), or by decreasing carbohydrate feeding of the cells.

The scientists found that, under conditions where they decreased the levels of CtBP, DNA repair increased and the cells developed stability and growth control. They determined that gene pathways targeted by CtBP were also disrupted in more aggressive breast cancers. Moreover, patients with high levels of CtBP in their tumors had shortened survival. And they showed that a small molecular inhibitor previously shown to bind to CtBP was able to reverse the gene-repressive effects of CtBP in breast cancer cells even under conditions of high carbohydrate feeding.

"Our new work suggests that targeting CtBP may provide a way of treating breast cancer and possibly preventing breast cancer," said Gardner. "Research should continue to focus on the link between obesity, CtBP and breast cancer. This will require more population-based studies and multi-disciplinary teams of scientist to investigate these links."

This project was funded by NCI project number 1Z01BC010847-01.


Story Source:

The above story is based on materials provided by National Cancer Institute (NCI) at NIH. Note: Materials may be edited for content and length.


Journal Reference:

  1. Li-Jun Di, Jung S. Byun, Madeline M. Wong, Clay Wakano, Tara Taylor, Sven Bilke, Songjoon Baek, Kent Hunter, Howard Yang, Maxwell Lee, Cecilia Zvosec, Galina Khramtsova, Fan Cheng, Charles M. Perou, C. Ryan Miller, Rachel Raab, Olufunmilayo I. Olopade, Kevin Gardner. Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer. Nature Communications, 2013; 4: 1449 DOI: 10.1038/ncomms2438

Cite This Page:

National Cancer Institute (NCI) at NIH. "Molecular link between metabolism and breast cancer." ScienceDaily. ScienceDaily, 6 February 2013. <www.sciencedaily.com/releases/2013/02/130206141531.htm>.
National Cancer Institute (NCI) at NIH. (2013, February 6). Molecular link between metabolism and breast cancer. ScienceDaily. Retrieved November 26, 2014 from www.sciencedaily.com/releases/2013/02/130206141531.htm
National Cancer Institute (NCI) at NIH. "Molecular link between metabolism and breast cancer." ScienceDaily. www.sciencedaily.com/releases/2013/02/130206141531.htm (accessed November 26, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Wednesday, November 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com
From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Newsy (Nov. 25, 2014) Need another reason to eat yogurt every day? Researchers now say it could reduce a person's risk of developing type 2 diabetes. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins