MENUTranscription factor can stifle breast cancer suppressing gene
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ANN ARBOR, Michigan — A transcription factor known as Snail1 can act as a “molecular bypass” that diminishes the natural tumor suppressing action of a gene called p53 in breast cancer patients, a group of scientists led by the University of Michigan and China Pharmaceutical University have found.
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The researchers made the findings while trying to understand the role Snail1 played in breast cancer progression in patients with both normal and mutated copies of the p53 gene. The p53 gene is sometimes called a “guardian of the genome” because mutations in it are associated with the development of many human cancers. In breast cancer, however, most patients do not have mutations in their p53 genes and the manner in which tumor cells bypass its protective effects have remained unknown.
While examining patient outcome data, the scientists noticed the correlation between high Snail1 levels and accelerated disease progression in patients with normal p53 genes. Follow-up studies in a mouse model of human breast cancer showed that animals engineered to lack Snail1 developed both fewer and smaller tumors than their counterparts. Importantly, deleting Snail1 did not adversely affect mammary gland development, the researchers found.
“Most breast cancer patients have a normal p53 gene — only about 25 percent don’t. This research points toward the possibility that Snail1-p53 interactions might be modulated for therapeutic benefit in breast cancer and other types of cancer,” says study co-senior author Stephen J. Weiss, M.D., a research professor at the University of Michigan Life Sciences Institute and associate director for basic science research at the U-M Rogel Cancer Center.