Heparin-binding growth factor isolated from human prostatic extracts.
Prostatic tissue extracts from patients with benign prostatic hyperplasia (BPH) and prostatic carcinoma were fractionated using heparin-Sepharose chromatography. The mitogenic activity of eluted fractions on quiescent subconfluent Swiss Albino 3T3 fibroblasts was tested employing a tritiated-thymidine-incorporation assay. Two peaks of activity were consistently noted--one in the void volume and a second fraction which eluted with 1.3-1.6 M NaCl and contained the majority of the mitogenic activity. Both non-heparin- and heparin-binding fractions increased tritiated incorporation into a mouse osteoblast cell line (MC3T3), while only the heparin-binding fractions stimulated a human umbilical vein endothelial cell line (HUV). No increased uptake of thymidine was seen using a human prostatic carcinoma cell line (PC-3). Sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of lyophilized active fractions showed a persistent band at 17,500 daltons. The purified protein demonstrated angiogenic properties using the chick embryo chorioallantoic membrane (CAM) assay. Western blot analysis using antibodies specific to basic fibroblast growth factor (bFGF) or acidic FGF (aFGF) demonstrated that the former, but not the latter, bound to prostatic growth factor (PrGF), and inhibited its mitogenic activity as well. It appears that PrGF shares homology with basic fibroblast growth factors.
Mydlo
J H
JH
Urologic Oncology Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Bulbul
M A
MA
Richon
V M
VM
Heston
W D
WD
Fair
W R
WR
D000482:Allantois / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002823:Chorion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D016222:Fibroblast Growth Factor 2; D005347:Fibroblasts / Q000187:drug effects; D006133:Growth Substances / Q000032:analysis / Q000302:isolation & purification* / Q000494:pharmacology; D006493:Heparin / Q000032:analysis / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008297:Male; D051379:Mice; D008934:Mitogens / Q000032:analysis / Q000302:isolation & purification* / Q000494:pharmacology; D011467:Prostate / Q000032:analysis*
D006133:Growth Substances; D008934:Mitogens; D016222:Fibroblast Growth Factor 2; D006493:Heparin