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Loosen leash on cancer protein 'watchdog,' researchers say

p came together, Mendrysa said, they were primarily concerned with how they might stop their prospective protein watchdog from doing more harm than good.

"Research is turning up lots of possible inroads for combating disease these days, and other research teams had found that p53 was a good prospect for fighting cancer," she said. "With too little p53 protein, people and mice are more likely to develop cancer. But it's not a panacea. Embryonic mice with too much p53 in their systems don't survive gestation. Moreover, recent reports have suggested that high levels of p53 may accelerate aging. Having the wrong amount of p53 protein, therefore, leaves you with two potentially unappealing choices: Do you want to die early of cancer or die early from wearing your body out?"

The scientists theorized that the solution could lie with another protein the body produces naturally to keep p53 in check. This other protein, called Mdm2, keeps p53 inactive until it is needed, acting like a leash on a watchdog.

"p53 seems to be an important stress response gene that fights cancer when it works," Mendrysa said. "So we decided to see what we could do to increase p53's activity without completely cutting its Mdm2 leash."

The scientists spent three years creating a strain of genetically modified mouse that only produced about 20 percent of the normal amount of Mdm2 protein, which is far less than they would have produced under ordinary conditions. The mice were created to answer a twofold question: Could increasing their levels of p53 delay or prevent tumor formation in living creatures, and would there be any negative consequences to the increase?

"We were primarily interested in the second part of the question when we began," Mendrysa said. "These mice had a family trait that typically made them develop cancerous lesions in their intestines, but our main goal was to see whether p53 sped up the aging process. Fortunately, we got more kinds of go
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Source:Purdue University


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