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Growth factor signals influence balance between normal growth and cancerous growth

r of body growth during childhood. These hormones continue to have important health effects during adulthood, after growth is done.

IGF-I is also of considerable interest to cancer researchers, because of mounting evidence that high levels of the protein contribute to cancer risk. One of the study's co-authors, oncologist Wafik El-Deiry, M.D., Ph.D., of the University of Pennsylvania, is internationally prominent for his studies of the p53 protein. "This work provides a novel and important insight into the regulation of growth by the major tumor suppressor p53," Dr El-Deiry said. He added, "For years we've known that p53 regulates another binding protein, IGBFP-3, to inhibit IGF signaling, but now we know that was the tip of the iceberg, as p53 appears to regulate the IGF axis at multiple nodes. It took collaboration between an endocrinologist and a medical oncologist to break this new ground, which has impact on both fields."

"We have no evidence now that either growth hormone or IGF-I actually causes cancer, but IGF-I may contribute to cancer progression and aggressiveness," said Dr. Grimberg. "IGF-I doesn't ignite the fire; it fuels it." At each stage that cancer progresses, she added, "IGF signaling can stimulate cells to behave more dangerously."

The study may have implications for patients receiving growth hormone or other growth-promoting therapies. Recombinant human growth hormone has been prescribed for the past 21 years for children with deficiency of normal growth hormone, to avoid abnormally short stature. However, in a controversial usage, that growth hormone is also prescribed for some short but healthy children with normal IGF-I levels to increase their height. "Excess levels of growth hormone and IGF-I may have long-term health risks," said Dr. Grimberg. "This study shows the interactions among pathways affecting growth and cancer are more complex than we have previously appreciated."

Better understanding of t
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Contact: John Ascenzi
Ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
9-Nov-2006


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