What is it about?

The bioavailability of IGF-I is controlled by the binding protein, IGF binding protein-3 (IGFBP-3). In addition, IGFBP-3 is a strong anti-proliferative protein that provokes apoptosis and inhibits cell proliferation in prostate cancer. We conducted this study to investigate the association between IGFBP-3 gene polymorphism and serum levels of IGF-I and IGFBP-3 and the incidence of prostate cancer (PCa) and benign prostatic hyperplasia (BPH).

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Why is it important?

With lifetime risk of 17%, prostate cancer (PCa) is the second most common cancer in men, and its incidence is still increasing.. Its molecular pathogenesis is being unraveled, and there is emerging evidence that polymorphic genes may modulate effects of endogenous androgens or environmental toxicants on PCa risk. Insulin like growth factor I (IGF-I) is secreted mainly by the liver. It modulates growth and development, and promotes cellular proliferation, survival and differentiation. In addition to stimulating cell proliferation, IGFs also inhibit the cellular apoptotic properties, thereby facilitating the cell growth. The effects of IGFs on cell proliferation and apoptosis are mediated via a specific cell membrane receptor, insulin-like growth factor-I receptor (IGF-IR). The interactions between IGFs and IGF-IRs are regulated by one of six binding proteins. Among this family, the most abundant binding protein in human serum is IGFBP-3.


Although it is usually assumed that the circulating concentrations of IGFs might be surrogates for IGF-I receptor signaling, the biological actions of IGFs are regulated by a complex system consisted of multiple IGFBPs. Higher circulating levels of IGFBPs might increase IGF concentrations by increasing half-lives, but due to decreased bioavailable IGF-I, not reflect an increase in receptor activation in tissue level. IGFBP-3 can stimulate apoptosis in human PCa cells directly, and preventing them from activating IGF-I receptors. The increased level of IGFBP-3 is associated with increased pro-apoptotic proteins. IGFBP-3 induces early apoptosis and has potential tumor suppressive effect in PCa. In addition, IGFBP-3 is known to function normally as an inhibitor of the IGF's action by blocking the binding of IGF to its receptor. Hence, this might explain why the PCa risk was more strongly associated with C allele in this study. We also compared IGF-1/IGFBP-3 molar ratios between the groups.

Dr Mohammad Reza Safarinejad
University of Medical Sceices

Read the Original

This page is a summary of: Relationship of insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) gene polymorphism with the susceptibility to development of prostate cancer and influence on serum levels of IGF-I, and IGFBP-3, Growth Hormone & IGF Research, June 2011, Elsevier, DOI: 10.1016/j.ghir.2011.03.008.
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