INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-2 AND PROTEIN-3 EXPRESSIONIN BENIGN HUMAN PROSTATE EPITHELIUM, PROSTATE INTRAEPITHELIAL NEOPLASIA, AND ADENOCARCINOMA OF THE PROSTATE

Insulin-Like growth factor (IGF)-binding proteins (IGFBPs) modulate th e activity of IGFs. In vitro human prostate epithelial cells secrete I GFBP-2 and -3. In vivo IGFBP-2 is increased, and IGFBP-3 is decreased in the serum of patients with prostate cancer. Immunohistochemistry an d in situ hybridization were performed to compare the expression of IG PBP-2 and -3 in vivo in prostate tissue containing benign epithelium, high grade prostate intraepithelial neoplasia (PIN), and adenocarcinom a. Immunoreactivity and messenger ribonucleic acid (mRNA) hybridizatio n signals for IGFBP-2 and -3 were localized to epithelial cells. IGFBP -2 immunostaining intensity was significantly increased in PIN regions compared to that in normal epithelium and was further increased in ma lignant cells. IGFBP-3 mRNA was also significantly increased in PIN an d cancer cells. IGFBP-3 immunoreactivity was significantly increased i n PIN regions compared to normal epithelium; however, IGFBP-3 protein was significantly decreased in malignant cells. IGFBP-2 mRNA remained virtually unchanged in benign epithelium, PIN, and adenocarcinoma cell s. These results demonstrate that increased IGFBP-2 protein in PIN and malignant cells is probably due to increased mRNA expression. However , levels of IGFBP-3 protein may be due to pre- and/or posttranslationa l mechanisms, including proteolysis. The changes in IGFBP-2 and -3 pro tein levels in prostate tissue are in agreement with serum changes rep orted in patients with prostate cancer.