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Growth factor receptor signaling critical to intestinal tumor development, studies show

CHAPEL HILL Scientists at the University of North Carolina at Chapel Hill and Vanderbilt University say they have uncovered a major clue to what causes and promotes development of intestinal tumors.

Working with laboratory mice, the researchers found that a molecule called epidermal growth factor receptor (Egfr) is necessary for most intestinal tumors to form. Their work also suggests that a drug or genetic manipulation that inhibits the receptors chemical signaling machinery should help treat advanced colorectal cancers in humans one day.

A report on the findings appears online today (Jan. 29) in the latest edition of the Proceedings of the National Academy of Sciences. Authors include doctoral student Reade B. Roberts and Dr. David W. Threadgill, assistant professor of genetics, both at the UNC School of Medicines Lineberger Comprehensive Cancer Center, and Dr. Robert J. Coffey, a cell biologist at Vanderbilt.

This Egfr receptor is very important to all kinds of tissues and organs, but there hasnt been any genetic proof in whole animals that it could affect a major cancer like colon cancer, Reade said. We think this work represents proof because it relied on genetic experiments that were highly controlled compared with just injecting mice with drugs and hoping that they would affect the receptor.

At UNC, the researchers studied two kinds of mice. They engineered one set to include a mutation called Apc-Min, which produces both human and mouse intestinal cancers, and another mutation known as waved 2, in which the Egfr was partially impaired. The other mice, litter mates of the first group, bore the same Apc-Min mutation, but also had normal Egfr genes.

Within three months, the first group developed 90 percent fewer intestinal polyps than the second, which showed that Egfr signaling was critical to intestinal tumor formation, scientists found. Some of the first group developed no tumors at all.

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Contact: David Williamson
david_williamson@unc.edu
919-962-8596
University of North Carolina at Chapel Hill
29-Jan-2002


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