Insulin-like growth factor-binding protein-2 and -3 expression in benign human prostate epithelium, prostate intraepithelial neoplasia, and adenocarcinoma of the prostate.
Insulin-like growth factor (IGF)-binding proteins (IGFBPs) modulate the activity of IGFs. In vitro human prostate epithelial cells secrete IGFBP-2 and -3. In vivo IGFBP-2 is increased, and IGFBP-3 is decreased in the serum of patients with prostate cancer. Immunohistochemistry and in situ hybridization were performed to compare the expression of IGFBP-2 and -3 in vivo in prostate tissue containing benign epithelium, high grade prostate intraepithelial neoplasia (PIN), and adenocarcinoma. Immunoreactivity and messenger ribonucleic acid (mRNA) hybridization 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 malignant cells. IGFBP-2 mRNA was also significantly increased in PIN and cancer cells. IGFBP-3 immunoreactivity was significantly increased in PIN regions compared to normal epithelium; however, IGFBP-3 protein was significantly decreased in malignant cells. IGFBP-3 mRNA remained virtually unchanged in benign epithelium, PIN, and adenocarcinoma cells. 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 posttranslational mechanisms, including proteolysis. The changes in IGFBP-2 and -3 protein levels in prostatic tissue are in agreement with serum changes reported in patients with prostate cancer.
Research Service, Veterans Affairs Medical Center, Seattle, Washington 98108, USA.
M K
MK
Tennant
J B
JB
Thrasher
P A
PA
Twomey
R S
RS
Birnbaum
S R
SR
Plymate
D000230:Adenocarcinoma / Q000737:chemistry*; D000368:Aged; D004848:Epithelium / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000032:analysis* / Q000235:genetics; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis* / Q000235:genetics; D007633:Keratins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000737:chemistry*; D017430:Prostate-Specific Antigen / Q000032:analysis; D019048:Prostatic Intraepithelial Neoplasia / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis
D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D007633:Keratins; D017430:Prostate-Specific Antigen