Influence of transforming growth factor beta 1 and other growth factors on basic fibroblast growth factor level and proliferation of cultured human prostate-derived fibroblasts.
Basic fibroblast growth factor (bFGF) has been identified in the human prostate. The level of bFGF has been reported to be elevated in benign prostatic hyperplasia (BPH), compared with normal prostate, suggesting that the growth factor may play a role in this disease of the prostate. Basic FGF is a mitogen for cultured human prostate-derived fibroblasts (PF). PF also synthesize bFGF, suggesting that growth regulation of these cells may be under autocrine control. The current study was undertaken to identify factors that affect PF proliferation and bFGF expression. Transforming growth factor beta 1 (TGF-beta 1) inhibited PF proliferation. The inhibition by TGF-beta 1 was partially overcome by bFGF but not by epidermal growth factor (EGF), platelet-derived growth factor (PDGF), insulin-like growth factor type 1 (IGF-1), or insulin. Incubation of PF with TGF-beta 1 increased bFGF mRNA and immunoreactive bFGF levels in a dose- and time-dependent fashion. None of the other growth factor studies affected bFGF levels. PF were also found to express TGF-beta 1 mRNA, the level of which was increased two- to fivefold by TGF-beta 1. These observations suggest that PF proliferation is controlled by the interaction of two different growth factors. It is possible that bFGF/TGF-beta imbalance in favor of cell proliferation promotes prostatic stromal hyperplasia.
Story
M T
MT
Department of Urology, Medical College of Wisconsin, Milwaukee 53226.
Hopp
K A
KA
Meier
D A
DA
Begun
F P
FP
Lawson
R K
RK
D001798:Blood Proteins / Q000502:physiology; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011467:Prostate / Q000166:cytology*; D011470:Prostatic Hyperplasia / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D001798:Blood Proteins; D003470:Culture Media; D006133:Growth Substances; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2