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Dec 11, 2007

Epigenetic Cancers Are Spurred by Growth Factors

  • Researchers at Johns Hopkins say that cancers arising from epigenetic changes develop by becoming addicted to certain growth factors. They believe that blocking these factors can prevent cancer growth. 

    The gene for growth factor IGF-II (insulin-like growth factor two) is one of several in the human genome that is controlled by imprinting. Normally, the IGF-II gene from your father is turned on and the one from your mother is turned off. Loss of this imprinting causes the activation of the maternal copy, leading to activation of both copies of the IGF-II gene, which has been associated with a fivefold increase of intestinal tumors in people.

    The Hopkins team tested mouse cells with imprinting intact and compared them to cells that have both copies of IGF-II activated. They found that normally imprinted cells respond to normal doses of growth factor and recover within 90 minutes. However, cells that had lost imprinting were activated by the smallest doses and continued to stay activated for more than 120 minutes.

    “It’s like they were on a hair trigger, which was totally counterintuitive to what we might have predicted,” says Andre Levchenko, Ph.D., an assistant professor of biomedical engineering at Hopkins and co-director of the study. “You would expect in cells that have lost imprinting and therefore have twice the amount of gene product, that it would take higher doses to activate the cell. In fact, the cell becomes hypersensitized while having too much IGF-II around.”

    The researchers then gave mice that were created to develop colon cancer a drug that specifically blocks a cell’s ability to respond to IGF-II. These mice developed 70% fewer precancerous lesions than mice without treatment.

    The study will be published online in next week’s Early Edition of the Proceedings of the National Academies of Sciences.



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