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Epidermal growth factor and platelet-derived growth factor regulate the activity of the insulin-like growth factor I
1Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Abstract:
The expression of insulin-like growth factor I (IGF-I) is regulated by hormones, oncogenes, and other growth factors, and is markedly decreased or even absent in senescent human diploid fibroblasts. In previous articles, we have reported that the SV40 large T antigen increases the production of IGF-I and that the expression of the IGF-I gene is negatively regulated by an E2F binding site in the IGF-I promoter. We have now investigated the activity of the IGF-I promoter, in response to stimulation of cells by either PDGF or EGF. Both growth factors stimulate the activity of the IGF-I promoter, indicating that they regulate the levels of expression of IGF-I. When the E2F binding sequence in the IGF-I promoter is mutated, the IGF-I promoter is constitutively active and no longer responds to the action of growth factors.