Researchers Find Key Genetic Driver for Rare Type of Triple-Negative Breast Cancer

For more than a decade, Celina Kleer, M.D., has been studying how a poorly understood protein called CCN6 affects breast cancer. To learn more about its role in breast cancer development, Dr. Kleer's lab designed a special mouse model - which led to something unexpected. The scientists deleted CCN6 from the mammary gland in the mice. This type of model allows researchers to study effects specific to the loss of the protein. As Dr.Kleer and her team checked in at different ages, they found delayed development and mammary glands that did not develop properly. "After a year, the mice started to form mammary gland tumors. These tumors looked identical to human metaplastic breast cancer, with the same characteristics. That was very exciting," says Dr. Kleer, Harold A. Oberman Collegiate Professor of Pathology and Director of the Breast Pathology Program at the University of Michigan Comprehensive Cancer Center. Metaplastic breast cancer is a very rare and aggressive subtype of triple-negative breast cancer - a type considered rare and aggressive of its own. Up to 20 percent of all breast cancers are triple-negative. Only 1 percent are metaplastic. "Metaplastic breast cancers are challenging to diagnose and treat. In part, the difficulties stem from the lack of mouse models to study this disease," Dr. Kleer says. So not only did Dr, Kleer gain a better understanding of CCN6, but her lab's findings open the door to a better understanding of this very challenging subtype of breast cancer. The study was published on November 7, 2016 in Oncogene. The article is titled "MMTV-cre;Ccn6 Knockout Mice Develop Tumors Recapitulating Human Metaplastic Breast Carcinomas." "Our hypothesis, based on years of experiments in our lab, was that knocking out this gene would induce breast cancer.
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