2/21/2007 6:41:06 PM article from Cancer World.org
http://www.cancerworld.org/home.asp
New gene discovery that may prevent cancer
One of the key areas of cancer research is to identify the exact location of oncogenes and tumour suppressor genes. These genes can either accelerate cancer development or, when damaged, permit unbridled cell growth.
American scientists at Cold Spring Harbor Laboratory and Stanford University have found a critical tumour suppressor gene, and have also revealed a master switch for a tumour suppressive network. The study published in the February issue of Cell will enable scientists to develop more targeted and effective cancer therapy.
The scientists identified CHD5, a protein that prevents cancer, as a novel tumour suppressor, mapping to a specific portion of chromosome 1 known as 1p36. When CHD5 is not doing its job, the machinery within our cells that normally prevents cancer is switched off. The ability of CHD5 to function as a master switch for a tumour suppressive network suggests that this gene is responsible for a large number of diverse forms of human cancers. Associate Professor Alea Mills, Ph.D. lead study author explains, “CHD5 functions like a circuit breaker that regulates the tumour-preventing power in our cells—when it blows, cancer occurs”. Modulation of CHD5 activity may provide novel strategies for better design of more effective cancer therapies. This gene has remained a mystery until the discovery.
After they located the region where the tumour suppressor resided, the scientists sought to identify which genes in that area were responsible for tumour suppression. Their results showed that reducing expression of a single gene-CHD5-made cells that had been rendered slow growing by adding an extra copy of the region, grow like normal cells.
The study’s findings show that deletion of a part of 1p36 causes cancer and increased “dosage” of CHD5 triggers extra tumour suppression. One extra dose, or copy, caused cells to either stop dividing or to undergo cell suicide by switching on a battery of potent tumour protective machinery. This work indicates that drugs that switch on CHD5 may provide a way to treat many types of human cancer.
The scientists worked with mouse models which enabled them to investigate the gains and losses of the chromosome segment corresponding to human 1p36. To extend the research to human cancer, the researchers studied whether CHD5 also functioned as a tumour suppressor in humans. They discovered that glioma, a specific form of brain tumour, frequently had deletion of CHD5, demonstrating the important role of CHD5 in human cancer.
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Sources: Cell 128, February 9, 2007 http://www.cell.com/content/article/abstract?uid=PIIS0092867407000530 Bagchi A., Papazoglu C., Wu Y., Capurso D., Brodt M., Francis D., Bredel M., Vogel H., Mills A.A. (2007) CHD5 is a tumour suppressor at human 1p36.
Cold Spring Harbor Laboratory.
Notes: Cold Spring Harbor Laboratory is a private, non-profit research and education institution dedicated to exploring molecular biology and genetics in order to advance the understanding and ability to diagnose and treat cancers, neurological diseases, and other causes of human suffering.
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