Navigation Links
UNC scientists find potential cause for deadly breast cancer relapse

CHAPEL HILL, N.C. Researchers at the UNC School of Medicine, working with cell lines in a lab, have discovered why some of the most aggressive and fatal breast cancer cells are resistant to chemotherapy, and UNC scientists are developing ways to overcome such resistance.

Adriana S. Beltran, PhD, a research assistant professor in the department of pharmacology, found that the protein Engrailed 1 is overexpressed in basal-like carcinomas and designed a chain of amino acids to shut down the protein and kill basal-like tumors in the lab.

"Patients with basal-like breast cancer tend to initially respond well to chemotherapy, but it's common for patients to relapse even more aggressively," said Beltran, the first author of a paper published in the journal Oncogene. "We believe that relapse is caused by a small number of cancer cells that have stem cell properties that allow them to survive chemotherapy. In these cells we've identified the overexpression of Engrailed 1."

Beltran and her colleagues UNC pharmacologist Lee Graves, PhD, and former UNC pharmacologist Pilar Blancafort, PhD discovered that Engrailed 1 is not involved in the rapid proliferation of cells that cause tumor growth. Nor is Engrailed 1 present in luminal tumors the most common form of breast cancer. The culprit protein only appears in basal-like breast cancer.

In fact, Engrailed 1 is normally confined to the brain, where it protects neurons from cell death and helps maintain their normal activity. The absence of the protein in the brain has been linked to the onset of Parkinson's disease. But there is no known function of Engrailed 1 within breast tissue.

"We think that Engrailed 1 confers protective features to breast cancer cells, similar to the features observed in long-lived neurons," Beltran said. "This may explain why these cells survive and become resistant to chemotherapy in our experiments."

The researchers found Engrailed 1 through a series of experiments designed to find genes highly expressed in basal-like cells but not in luminal breast cancers. They discovered that Engrailed 1was most highly expressed in cell lines isolated from inflammatory breast cancer. Working with the UNC Michael Hooker Proteomics Center, Beltran and colleagues also determined that Engrailed 1 was associated with the gene EPRS, which expresses an enzyme that controls messenger RNA and protein synthesis, particularly in proteins involved with inflammation.

"Inflammation is associated with cancer development," Beltran said. "It's interesting to us that Engrailed 1, alone, is able to control inflammatory responses that may promote more aggressive forms of cancer."

Why Engrailed 1 is manifested in cancerous breast tissue remains a mystery. "Nature seems to always find a way," Beltran said. "Cancer cells are part of nature; everything in nature strives to survive."

But Beltran and her colleagues might have found a way to stop Engrailed 1. After studying how Engrailed 1 binds to DNA and other proteins, the researchers created a synthetic peptide a chain of amino acids that can stifle the binding power of Engrailed 1. In cell lines not in animals or patients Beltran and colleagues used their peptide to disrupt Engrailed 1 from binding to its protein partners and DNA.

"Cancer cells need Engrailed 1 to live," Beltran said. "The peptide abolishes all interactions of Engrailed 1, and as a consequence Engrailed 1 cannot perform its functions, causing rapid cell death of the cancer cell.

"The goal now is to validate our findings in animal models."

If Engrailed 1 turns out to be as critical to basal-like metastasis as it seems from this basic research, then a drug could be developed to fight cancer relapse in some of most deadly forms of breast cancer.


Contact: Mark Derewicz
University of North Carolina Health Care

Related medicine news :

1. Scientists solving the mystery of human consciousness
2. Scientists uncover multiple faces of deadly breast cancer
3. Scientists identify major source of cells defense against oxidative stress
4. Scientists tailor cell surface targeting system to hit organelle ZIP codes
5. Scientists rewrite rulebook on breast cancer in landmark global study
6. Warwick scientists uncover how checkpoint proteins bind chromosomes
7. NIH scientists link quickly spreading gene to Asian MRSA epidemic
8. Joslin scientists identify important mechanism that affects the aging process
9. Scripps Research scientists show how memory B cells stay in class to fight different infections
10. Scientists Map Melanomas Genome
11. A*STAR scientists discover switch to boost anti-viral response to fight infectious diseases
Post Your Comments:
(Date:6/26/2016)... ... June 27, 2016 , ... Quality metrics are proliferating in cancer care, ... remain in the eye of the beholder, according to experts who offered insights and ... Journal of Managed Care. For the full issue, click here . , For ...
(Date:6/26/2016)... ... June 26, 2016 , ... Brent Kasmer, a legally blind and certified personal trainer is ... a fitness app. The fitness app plans to fix the two major problems leading the ... one size fits all type program , They don’t eliminate all the reasons ...
(Date:6/25/2016)... ... June 25, 2016 , ... The temporary closing of Bruton Memorial Library on June 21 ... brings up a new, often overlooked aspect of head lice: the parasite’s ability to live ... not a common occurrence, but a necessary one in the event that lice have simply ...
(Date:6/25/2016)... City, Oklahoma (PRWEB) , ... June 25, 2016 ... ... helping both athletes and non-athletes recover from injury. Recently, he has implemented orthobiologic ... the Oklahoma City area —Johnson is one of the first doctors to perform ...
(Date:6/24/2016)... Michigan (PRWEB) , ... June 24, 2016 , ... Those ... deal with these feelings, many turn to unhealthy avenues, such as drug or alcohol ... of Marne, Michigan, has released tools for healthy coping following a traumatic event. , ...
Breaking Medicine News(10 mins):
(Date:6/26/2016)... , June 27, 2016 Jazz Pharmaceuticals plc ... period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, ... of Celator Pharmaceuticals, Inc. ("Celator"; Nasdaq: CPXX ... (Eastern Daylight Time). As previously announced on ... a definitive merger agreement under which Jazz Pharmaceuticals has ...
(Date:6/24/2016)... , June 24, 2016  Collagen Matrix, Inc., ... development and manufacturing of collagen and mineral based ... today that Bill Messer has joined ... to further leverage the growing portfolio of oral ... Bill joins the Collagen Matrix executive ...
(Date:6/24/2016)... , June 24, 2016 ... the "Structural Electronics 2015-2025: Applications, Technologies, Forecasts" ... In-Mold Electronics, Smart Skin, Structural ... Structural electronics involves electronic and/or ... protective structures, replacing dumb structures such as vehicle ...
Breaking Medicine Technology: