HOUSTON - The molecular machinery that switches on a gene known to cause breast cancer to spread and invade other organs has been identified by an international team led by scientists at The University of Texas M. D. Anderson Cancer Center. The paper was published Sunday in Nature Cell Biology's advanced online publication.
The discovery provides a target-rich environment for development of drugs to thwart expression of the RhoA gene, according to Hui-Kuan Lin, Ph.D., the paper's senior author and an assistant professor in M. D. Anderson's Department of Molecular and Cellular Oncology. RhoA overexpression has been implicated in cancer metastasis.
"There are four components to this complex, which starts RhoA expression by transcribing the gene, and we found that all of them are important to metastasis," Lin said. "Knock down any one of the four, and you can stop breast cancer metastasis by preventing RhoA expression."
Researchers built their case with a series of laboratory experiments on cell lines, followed by confirmation in a mouse model of breast cancer metastasis and then analysis of 64 prostate cancer tumors that showed overexpression of RhoA or three of its transcription complex components were strongly correlated with metastatic disease.
Transcription is the first step on a gene's path to expressing its protein. Transcription factors bind to the promoter region of the gene, causing a copy of RNA to be made from the DNA of the gene. The RNA is then translated into the corresponding protein.
The team first established the Myc protein as a transcription factor that binds to RhoA's promoter region. Knocking down Myc in cancer cell lines decreased RhoA expression, cell migration and invasion, while Myc overexpression increased all three.
Next, they found that the Skp2 overexpression also results in more RhoA, and that both Skp2 and Myc were required for the metastasis-producing RhoA to be overe
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center