The study reviewed here found that a gene called metadherin (MTDH) may cause some breast cancers to spread to distant locations in the body (metastasize). MTDH also may cause some breast cancers to stop responding to chemotherapy.
Other research has found that one or more genes are associated with a poor prognosis for some breast cancers. MTDH is one of these genes. The study reviewed here looked at how some of these genes acted in human breast cancer tissue that was put into mice. Breast cancer tissue with an active MTDH gene spread to distant locations (metastasized) seven times more than breast cancers with an inactive MTDH gene. The other genes looked at in this study didn't seem to affect breast cancer spread.
It's thought that the MTDH gene affects about 30% to 40% of all breast cancers. Researchers aren't sure how an active MTDH gene influences the spread of breast cancer or chemotherapy resistance.
While encouraging, these results are early results. The research was done on human tissue implanted in mice. More research is needed to understand how the MTDH gene affects breast cancer. Still, this research can offer clues to how breast cancer spreads and responds to treatment. In the future, researchers may discover therapies that target and block the MTDH gene, which may help treat breast cancer.
Stay tuned to Breastcancer.org for the latest news on research that may lead to better ways to prevent, diagnose, and treat breast cancer.
PRINCETON, N.J., Jan. 5 (MedPage Today) -- A gene associated with poor-prognosis breast cancer has been identified by genomic profiling studies that may point to a new therapeutic target, investigators here reported.
Functional studies of the metastasis gene metadherin (MTDH) showed the gene promotes chemoresistance, as well as metastasis, in 30% to 40% of breast cancers, Yibin Kang, Ph.D., of Princeton University, and colleagues reported in the Jan. 6 issue of Cancer Cell.
The discovery confirms a long-held suspicion about the existence of such a gene in the 8q22 region of chromosome 8.
"Inhibiting this gene in breast cancer patients will simultaneously achieve two important goals: reduce the chance of recurrence, and, at the same time, decrease the risk of metastatic dissemination," Dr. Kang said in a statement. "Clinically, these are the two major reasons why breast cancer patients die from the disease."
Cancer researchers had known for some time that an increased 8q22 copy number (genomic gain) confers a poor prognosis in breast cancer. However, the mechanisms linking the region to poor prognosis and metastasis had remained unclear.
In the current study, investigators developed a computer algorithm to predict recurrent DNA copy number alterations affecting regional gene expression.
They then used fluorescence in situ hybridization and genomic DNA quantitative polymerase chain reaction technology to confirm 8q22 genomic gain in several sets of breast tumor specimens.
The studies revealed gain in about 30% of specimens, which was consistent with the computer algorithm's predictions.
The investigators also examined expression patterns of three other genes (PTDSS1, MTDH, and LAPTM4?) in the 8q22 region. They found a strong correlation between the genes' expression and 8q22 copy numbers.
In particular, analysis of a panel of breast cancer cell lines demonstrated correlation between 8q22 gain and higher levels of MTDH expression.
By studying mice implanted with breast cancer xenografts, the authors found that MTDH overexpression accelerated development of lung metastasis and decreased survival.
As compared with controls, tumors with MTDH overexpression had a sevenfold increase in metastasis burden. In contrast, overexpression of other genes did not increase metastatic potential.
Additional studies with mice showed that inhibition of MTDH expression significantly reduced lung metastasis burden and increased survival.
"Not only has a new metastasis gene been identified, but this also is one of a few such genes for which the exact mode of action has been elucidated," said co-author Michael Reiss, M.D., of the University of Medicine and Dentistry of New Jersey in New Brunswick. "That gives us a real shot at developing a drug that will inhibit metastasis."
The study was supported by the Department of Defense Era of Hope Scholar Award Program, the National Institutes of Health, the American Cancer Society, the Susan G. Komen Foundation, and the New Jersey Commission on Cancer Research.
The authors reported no disclosures.
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