"The suppression of two genes reduces breast cancer tumor formation and spread by interfering with blood vessel formation and recruitment, according to new research from Houston Methodist, Weill Cornell Medical College and other institutions. The findings in the Proceedings of the National Academy of Sciences may help medical researchers identify effective drug targets for triple negative breast cancer (TNBC).
The genes, MLF2 (myeloid leukemia factor 2) and RPL39 (a ribosomal protein), were found to most profoundly affect the production of nitric oxide synthase, which helps regulate blood vessel behavior and could be crucial to the recruitment of new blood vessels to growing tumors. These genes influence the spread of TNBC throughout the body, and have not so far been linked with breast cancer.
"We have found two unique genes that may affect the most lethal type of breast cancer," said principal investigator and Houston Methodist Cancer Center Director Dr. Jenny Chang, who is also a professor of medicine at Weill Cornell Medical College. "Most importantly, by knowing how these genes function, we have drugs that can block nitric oxide signaling."
About 42,000 new cases of triple negative breast cancer are diagnosed in the United States each year, about 20 percent of all breast cancer diagnoses. Patients typically relapse within one to three years of being treated. TNBC is distinguished from other breast cancers in that it does not express the genes for estrogen receptors, progesterone receptors, and Her2/neu and is frequently harder to treat than other forms of the disease.
By suppressing close to 500 TNBC-related genes, Chang's group found interference was strongest with MLF2 and RPL39 in triple negative breast cancer model tissue. The scientists also learned that mutations in these genes in human patients were associated with worse survival in triple negative breast cancer patients."