Scientists identify molecular link between metabolism and breast cancer

February 6, 2013

(Medical Xpress)—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.

"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 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 expression in response to high . This explains, in part, why women who have hereditary mutations of 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 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 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 . This will require more population-based studies and multi-disciplinary teams of scientist to investigate these links."

Explore further: Endotrophin links obesity to breast cancer progression

More information: Gardner K, et al. Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer. Nature Communications. Feb. 5, 2013. DOI: 10.1038/ncomms2438

Related Stories

Endotrophin links obesity to breast cancer progression

October 8, 2012
Fat cells (adipocytes) surround breast tumors and contribute to tumor growth by expressing factors that aid oncogenesis. Col6 is a protein that is highly expressed in adipocytes and its expression is further increased in ...

Researchers discover that same gene has opposite effects in prostate, breast cancers

October 17, 2011
Researchers at Cleveland Clinic have discovered that a gene – known as an androgen receptor (AR) – is found in both prostate and breast cancers yet has opposite effects on these diseases.

Recommended for you

No dye: Cancer patients' gray hair darkened on immune drugs

July 21, 2017
Cancer patients' gray hair unexpectedly turned youthfully dark while taking novel drugs, and it has doctors scratching their heads.

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.