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Loosen leash on cancer protein 'watchdog,' researchers say

od news than we initially expected."

Mice with such a predisposition generally developed about 50 intestinal lesions within six months of birth, but mice modified for the study had only developed three or fewer within that time frame. Moreover, there was no sign that the mice had aged any faster than normal.

"We checked for the sort of characteristics that the elderly of many mammal species typically show - thinner skin, lower bone density, spinal hunching and the like," Mendrysa said. "We couldn't find any differences between them and normal mice. And their cancer rates were dramatically lower than expected, which turned out to be the more significant finding of the study."

Mendrysa said the results were an enlightening fundamental discovery about suppressing hereditary intestinal cancers. But she also said the work raised a number of questions that would need to be answered before the research could translate into human therapy.

"These mice were genetically modified at conception to produce higher p53 levels, which is quite a different treatment than just giving normal mice a pill," Mendrysa said. "Also, mice in our study are not subject to the same stresses as, for example, a person working on Wall Street. It remains to be seen whether higher p53, in conjunction with other factors such as stress, could still lead to negative consequences such as aging. We'll have to do a lot more work before this becomes a routine part of medicine's anticancer toolkit.

"Essentially, this study validates Mdm2 as a potentially powerful chemopreventative for some kinds of hereditary cancer, and, if used properly, it might perform well without elevating the risks of aging that other groups have found. The benefits seem to outweigh the risks.

"We'd like to expand the research and look into how Mdm2 and p53 affect other cancer predispositions. If we can find the right length for the leash, someday we may be able to find a way to specify i
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Source:Purdue University


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