U-M researchers identify gene involved in breast cancer

Updated 11:00 AM August 13, 2007

U-M researchers identify gene involved in breast cancer

By Nicole Fawcett
Comprehensive Cancer Center

Researchers at the 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 effectively can 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 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.

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.

"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, it's too early to tell," says study author Yang Liu, the Charles B. de Nancrede Professor of Surgery and professor of surgery at the Medical School and co-director of the cancer immunology program at the Comprehensive Cancer Center. Results of the study appear in the June issue of the journal Cell.

Initially, the researchers were studying FOXP3's role in autoimmune disease, when they noticed that female mice with one copy of the mutated form of the gene were developing breast cancer. Moreover, the tumors expressed high levels of ErbB2, the mouse equivalent of HER-2. Breast cancer is rare in mice, and ErbB2-positive breast cancer is even more rare.

"Given the significant role HER-2 plays in breast cancer and the widespread defects we found on FOXP3, it is likely that this gene play an important role in suppressing breast cancer," says Dr. Pan Zheng, associate professor of surgery and pathology at the Medical School.

More than 180,000 women will be diagnosed with breast cancer this year, and 40,900 will die from the disease, according to the American Cancer Society. For information about breast cancer and available genetic tests, go to www.mcancer.org or call the U-M Cancer AnswerLine at (800) 865-1125.

In addition to Zheng and Liu, U-M study authors were Lizhong Wang, Xing Chang, Huiming Zhang, Weiquan Li, Yan Liu, Yin Wang, Bae Keun Park and Cun-Yu Wang. Additional authors are Tao Zuo, Carl Morrison, Michael W.Y. Chan, Jin-Qing Liu, Chang-gone Liu, Rulong Shen, Xingluo Liu, Tiany Yang, and Tim Huang; with Richard Love from Ohio State University and Virginia Godfrey from the University of North Carolina, Chapel Hill.

Funding for the study was from the National Institutes of Health and U.S. Department of Defense.

U-M researchers identify gene involved in breast cancer

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