Scientists find a new function for breast cancer gene BRCA1:
Scientists at the National Cancer Institute (NCI) have uncovered a new function for BRCA1, a gene most commonly associated with hereditary breast and ovarian cancer. Working on mouse cells in the lab, they discovered that BRCA1 suppresses the expression of another gene that codes for a microRNA called miR-155, which is known to be cancer causing. These findings, published online Sept. 25, 2011, in Nature Medicine suggest that BRCA1 functions as a tumor suppressor not only by playing a role in DNA repair, as known previously, but also by silencing a gene that can cause cancer when over-expressed. When the scientists inactivated miR-155 in tumor cells in mice, it slowed down the growth of tumors. If the BRCA1-associated tumors are confirmed to be dependent upon miR-155, it may be possible to treat hereditary cancers by challenging them with agents that can inactivate mir-155.
The scientists also investigated precisely how BRCA1 silences miR-155 in cells. Shyam K. Sharan, Ph.D, head of the Genetics Cancer Susceptibility Section, Mouse Cancer Genetics Program, NCI-Frederick and Suhwan Chang, Ph.D., research fellow, found that BRCA1, through its interaction with another protein called histone deacetylase2, modifies the proteins (known as histones) that wrap around DNA and help maintain its structure. As a result of these modifications, DNA is prevented from expressing miR-155. If there is a defect in BRCA1, these modifications of DNA do not occur and miR-155 is over-expressed. Based on a strong correlation between BRCA1 mutation and miR-155 over-expression in tumors, the scientists also suggest that miR-155 could be used as a biomarker for BRCA1-deficient human tumors.
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