The expression of insulin-like growth factor binding proteins in human hepatocellular carcinoma

Insulin-like growth factors (IGF), IGF receptors and IGF binding proteins ( IGFBPs) play an important role in cell growth and differentiation. The live r is the major source of IGF-1 and at least two IGFBPs (IGFBP-1 and IGFBP-3 ). IGFBPs most often serve to attenuate the effects of IGF at the receptor level and thereby limit IGF-induced cell growth and differentiation. Althou gh changes in IGFBP expression have been described during controlled liver growth such as hepatic regeneration following partial hepatectomy, there is limited knowledge of IGFBPs gene expression in uncontrolled growth or hepa tocellular carcinoma. In the present study, we employed Northern blotting t echniques to document the expression of IGFBP-1, 3 and 4 in normal human li vers, cirrhotic and hepatocellular carcinoma tissues. The results revealed no differences in IGFBP-1, 3 and 4 mRNA levels between normal and cirrhotic tissues. However, the expression of all three IGFBPs mRNA were significant ly down regulated in hepatocellular carcinoma tissues. These findings are i n keeping with IGFBPs playing an important inhibitory role in the developme nt and/or growth of hepatocellular carcinoma in humans.