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Plant-derived molecules, genetic manipulation point to future chemoprevention methods

research suggests that reducing levels of the growth hormone IGF-1 could prove to be a promising method for preventing colon cancer from developing. It is also the first known study to successfully develop a way to examine depleted IGF-1 function in living animals.

Susan Olivo-Marston, Ph.D., a postdoctoral fellow at the NCI, and her colleagues found that mice that lacked a gene that ultimately resulted in drastically reduced IGF-1 in the livers of mice had nearly half the number of tumors seen in mice with normal IGF-1 levels. Specifically, they found that mice with normal IGF-1 levels had an average of 13 colon tumors, but the IGF-deficient mice had only 7.2 tumors on average. In addition, the colon tumors in IGF-deficient mice were less likely to be found in the proximal colon; 25 percent of tumors were in the proximal colon of deficient mice, compared to 60 percent in the control mouse colons.

Since IGF-1--in addition to its role in controlling the maximal, final growth of a young adult animal--also inhibits programmed cell death and stimulates colon epithelial cells, the scientists tested IGF-deficient mice for these cancer-causing characteristics. In fact, deficient mice had a decrease in proliferation in colon cells and an increase in apoptosis.

The researchers were presented with a significant challenge, in that directly knocking out expression of IGF-1 in mice resulted in severe developmental abnormalities and very low survival rates. Therefore, the researchers found an existing type of mouse that lacked a gene called igf1 in the liver. These mice are IGF-1 deficient, but develop normally and have a 75 percent reduction in circulating levels of IGF-1.

"High levels of IGF-1 have been associated with significant increases in colon cancer risk" said Olivo-Marston. "Since IGF-1 inhibits apoptosis and stimulates colon epithelium proliferation, we hypothesized that reducing, if not eliminating, its function could prove
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Source:American Association for Cancer Research


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