The scientists in this study addressed this problem by using an innovative computational biology approach. They re-analyzed massive clinical breast cancer databases and found that study after study showed one area in common -- a very small region in human chromosome 8 called 8q22. They found that this area of the chromosome is repeated many times in the genomes of poor-prognosis breast tumors. Some chromosomes contained as many as eight copies or "repeats" of the genetic segment. Most normal DNA sequences contain only two copies of a given gene, conveyed from the genomes of the male and female parents.
Next, the team studied breast tumor samples collected from patients at The Cancer Institute of New Jersey. In doing so, the researchers were able to validate the computational prediction, confirming that the genetic sequence identified in the database was overproduced in the DNA of the poor-prognosis tumor samples.
The researchers went on to discover that among a handful of genes in the 8q22 region, MTDH is responsible for the aggressive behavior of poor-prognosis tumors. They used recombinant DNA technology to enhance the expression of individual genes in the region, one by one, in breast tumor cells and tested their metastatic behavior in laboratory mice.
The scientists found that MTDH-overexpressing tumors are more likely to metastasize to the lungs, other vital organs and bones. Importantly, these tumors were also found to be more resistant to a wide range of chemotherapeutic agents, including paclitaxel, cisplatin and adriamycin. When researchers genetically altered the cancer cells to reduce the expression of MTDH, these tumor cells become less able to metastasize and more likely to be eliminated by chemotherapy agents.
"This is probably one of the first examples of
|Contact: Kitta MacPherson|