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Insulin-like growth factor binding protein 3 (IGFBP-3): a novel target of the tumor suppressor p53 inhibiting cell growth

The insulin-like growth factors (IGFs) have been known for a long time to play an important stimulatory role in cell growth. Their bioavailability is regulated by at least six IGF binding proteins. More recently, an inhibition of cell proliferation by one of these IGF binding proteins (IGFBP-3) has been observed. The growth inhibitory effect of IGFBP-3 could be mediated by inhibition of IGF-I. Nevertheless, experiments performed using fibroblasts devoid of IGF-I receptor (derived from IGF-I receptor knockout embryos) suggest that growth inhibition by IGFBP-3 could be independent of the IGF-I receptor (1). The human tumor suppressor protein p53 is critical for the regulation of the cell cycle in response to genotoxic stress. Deleterious mutations or loss of the p53 gene are observed in over half of all human tumors. It is also speculated that the upstream or downstream component of the p53 pathway could be altered in some of the

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