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
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University of North Carolina Health Care