Overexpressed Protein May Disrupt BRCA2 In Sporadic Breast, Ovarian Cancers

WASHINGTON (Reuters) - Researchers have identified a protein, EMSY, implicated in both familial and sporadic breast and ovarian cancers.

EMSY appears to disrupt the BRCA1 and BRCA2 genes, which are normally involved in DNA repair and transcriptional regulation, and may explain why some women without mutations in these genes develop breast cancer, according to a report in the November 26th issue of Cell.

To find the potential link between BRCA-associated and sporadic breast cancers, Dr. Tony Kouzarides from the Cancer Research U.K/Wellcome Trust Institute in Cambridge and colleagues evaluated 551 women with sporadic breast cancer. While their BRCA genes appeared normal, EMSY was overactive in some cases.

The researchers found that "EMSY maps to chromosome 11q13.5, a region known to be involved in breast and ovarian cancer." EMSY expression was also linked with "worse survival, specifically in node-negative breast cancer, suggesting that it may be of prognostic value."

The women whose EMSY protein was overactive had unusually aggressive breast cancer -- in fact, similar to women with BRCA2 mutations.

In several hundred Canadian breast cancer patients from British Columbia, women with overactive EMSY survived an average of 6.4 years, while those whose tumors were similar but without excess EMSY lived 14 years.

"Clearly, breast cancer with amplifications of EMSY are bad guys," Dr. Carlos Caldas, a University of Cambridge oncologist who worked on the study, said in a telephone interview.

EMSY was overactive in about 13% of sporadic cases of breast cancer and 17% of ovarian cancers, Dr. Caldas said. Both EMSY and BRCA seem to be DNA repair proteins. "Perhaps they interfere with each other," he speculated.

"The next step is to refine the function of the EMSY protein at the biochemical level," he added. "We want to identify what is special about these tumors, why they are so aggressive clinically."

Source: Cell 2003;115:523-535. [ Google search on this article ]

MeSH Headings: Biological Sciences : Biology : Breast Neoplasms : Gene Expression Regulation : Genetics : Genetics, Biochemical : Molecular Biology : Neoplasms : Neoplasms by Site : Genes, BRCA1 : Gene Silencing : Biological Sciences : Diseases