Rampant cancer. Mice with a single copy Working tumor suppressor Mus81 have prostate (left) and muscle (right) cancers, among others.
tumor suppressor genes are sentinels stand guard against cancer: knock them, and tumors may suddenly surface. Now researchers studying mice found a more potent suppressor genes tumor still -. The animals there are missing an amazing 50% chance of developing cancer
Tens of tumor suppressor genes have been identified, but most are poorly understood. Many, however, share one thing in common: The genes can not manage the damage to their DNA, and when mutated, they are the most likely cancer. Razqallah Hakem, a cancer biologist at the University of Toronto, Ontario, and colleagues studied normally a tumor suppressor called BRCA1 , variants that put women at high risk for breast cancer and ovarian. But recently, his attention was drawn to a mysterious gene that has been linked to cancer: Mus81 . Yeast lacking Mus81 were hypersensitive to radiation and other agents that damage DNA; in a yeast species, the gene appeared to be a crucial player in cell division.
team Hakem asked if Mus81 , with its sensitivity to DNA damage, could have a cancer link. To find out, the scientists raised mice lacking one or both copies of the gene. Only half of the animals with a good copy of Mus81 , and a quarter of those with no copies, remained healthy and survived a year. Tumors, especially lymphoma, raged through each of the diseased mice, reports the team in the June issue 18 Science . These mice were more likely to get tumors than mice lacking almost any other tumor suppressor, with the exception of the widely studied P53 gene, Hakim said.
The work also casts doubt on a widespread theory about the function of Mus81 . Yeast studies have suggested that Mus81 was critical for a specific step in cell division which is essential for chromosome recombination during reproduction. To the surprise of researchers, however, the missing animals one or two copies of Mus81 were fertile and produced normal sperm and egg cells. Apparently Mus81 works differently in mice.
" Mus81 really did play a crucial role" in suppressing tumors, says Stephen West, a biochemist at Cancer Research UK in London. It is particularly striking, he said, than mice with only one defective copy of Mus81 have cancer. Hakim said that came as a surprise to him, too. Although good copy of Mus81 can still make proteins, Hakim said was apparently not enough to ward off cancer.
Related Sites
Hakem and colleagues science article
homepage of Razqallah Hakem
Background on certain tumor suppressor genes
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