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Medicineworld.org: U-M researchers identify gene involved in breast cancer

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U-M researchers identify gene involved in breast cancer




Scientists at the University of Michigan Comprehensive Cancer Center have identified a gene associated with the development of an aggressive form of breast cancer.

The scientists observed 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 associated with cancer has been found on the X chromosome.



U-M researchers identify gene involved in breast cancer

When one copy of the FOXP3 gene is silenced, the scientists found in studying mice, 90 percent of the mice spontaneously developed malignant tumors. The scientists also looked at FOXP3 in human breast tissue cells, comparing malignant and non-malignant 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 scientists found FOXP3 to be a repressor of HER-2, a protein that typically marks a more aggressive form of breast cancer. The scientists believe FOXP3 suppresses the HER-2 gene. HER-2 can be activated by a number of different factors, but the scientists observed 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 scientists 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 scientists do not know if FOXP3 can predict breast cancer risk, like the BRCA1 and BRCA2 genes, both of which are associated with 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 therapy, 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 program at the U-M Comprehensive Cancer Center. Results of the study appear in the journal Cell.

Initially, the scientists were studying FOXP3s 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.

FOXP3 is the first X chromosome-linked gene that suppresses breast cancer and represses the HER-2/ErbB2 oncogene. 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 Pan Zheng, M.D., Ph.D., associate professor of surgery and pathology at the U-M Medical School.


Posted by: Janet    Source




Did you know?
Scientists at the University of Michigan Comprehensive Cancer Center have identified a gene associated with the development of an aggressive form of breast cancer. The scientists observed 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 associated with cancer has been found on the X chromosome.

Medicineworld.org: U-M researchers identify gene involved in breast cancer

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