ANN ARBOR, Mich. Researchers at the University of Michigan Comprehensive Cancer Center have identified a gene linked to the development of an aggressive form of breast cancer.

The researchers found that the gene, FOXP3, suppresses tumor growth. FOXP3 is located on the X chromosome, which means a single mutation can effectively silence the gene. This is unusual, as only one other gene linked to cancer has been found on the X chromosome.

When one copy of the FOXP3 gene is silenced, the researchers found in studying mice, 90 percent of the mice spontaneously developed cancerous tumors. The researchers also looked at FOXP3 in human breast tissue cells, comparing cancerous and non-cancerous cells. FOXP3 was found to be either deleted or mutated in a substantial portion of the cancer sample: about 80 percent of the cancer tissues studied did not express the gene at all.

In addition, the researchers found FOXP3 to be a repressor of HER-2, a protein that typically marks a more aggressive form of breast cancer. The researchers believe FOXP3 suppresses the HER-2 gene. HER-2 can be activated by many different factors, but the researchers found that when FOXP3 is normal, it keeps HER-2 levels low; when FOXP3 is missing or mutated, HER-2 levels are likely to rise.

The researchers have shown that FOXP3 was reduced or missing in about 80 percent of the more than 600 cases of breast cancer tissue examined. At this point, the researchers do not know if FOXP3 can predict breast cancer risk, like the BRCA1 and BRCA2 genes, both of which are linked to a higher risk of breast cancer.

FOXP3 defects promote cancer development. We do not know whether this is a genetic defect that puts women at higher risk. For treatment, this gene could be quite important, but for diagnosis, its too early to tell, says study author Yang Liu, Ph.D., deNancrede Professor of Surgery at the U-M Medical School and co-director of the cancer immunology prog
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Contact: Nicole Fawcett
nfawcett@umich.edu
734-764-2220
University of Michigan Health System
26-Jul-2007