Growth factor signals influence balance between normal growth and cancerous growth

For many biological processes, the Goldilocks Principle rules. You don't want too much, or too little, of something, you want it just right.

So it is with the body's delicate concentration of growth factors. Too much of a signaling protein called insulin-like growth factor-I (IGF-I) may fan the flames of cancer, while too little of the protein may cause short stature, dementia and osteoporosis, among other problems.

New research from The Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine deepens the understanding of how the growth hormone/IGF system is affected by another important actor: p53, the tumor suppressor gene that puts the brakes on cancer. The interplay of the two signaling pathways reinforces questions about the long-term risks of prescribing growth hormone and IGF-I to patients, at the same time that it may suggest a future new avenue for cancer therapy.

The study, which used cell cultures and mice, was published in the October issue of Cancer Biology & Therapy.

"It was already known that the tumor suppressor protein p53, which causes a cell to stop growing or to self-destruct, also acts on genes in the growth hormone/IGF axis to turn down IGF signaling," said pediatric endocrinologist and lead author Adda Grimberg, M.D., of The Children's Hospital of Philadelphia. "In this paper we showed that p53 increases production of insulin-like growth factor binding protein-2, an interaction that was not previously known." That protein, abbreviated as IGFBP-2, binds to IGF-I, and thus makes the growth factor less available to act on the body's tissues.

When the authors used genes to halt IGFBP-2 production by prostate cancer cells in culture, they found that p53 lost its ability to block IGF-I from activating one of its major signaling targets in those cells.

IGF-I is important because, along with naturally produced human growth hormone, it is the major regulato

Contact: John Ascenzi
Children's Hospital of Philadelphia

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