Differential expression of transforming growth factor-?1 and ?3 as well as C-FOS mRNA in normal human prostate, benign prostatic hyperplasia and prostatic cancer

1994 ◽  
Vol 12 (2) ◽  
Author(s):  
V.W. Merz ◽  
A.M. Arnold ◽  
U.E. Studer
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Growth Factor ◽  
Differential Expression ◽  
Prostatic Cancer ◽  
Transforming Growth Factor ◽  
Prostatic Hyperplasia ◽  
Human Prostate ◽  
Normal Human

scholarly journals Transforming growth factor-beta induces growth inhibition and IGF-binding protein-3 production in prostatic stromal cells: abnormalities in cells cultured from benign prostatic hyperplasia tissues

2000 ◽  
Vol 164 (2) ◽  
pp. 215-223 ◽  
Author(s):  
P Cohen ◽  
SE Nunn ◽  
DM Peehl
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Growth Factor ◽  
Growth Inhibition ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Fold Increase ◽  
Prostatic Hyperplasia ◽  
Igf Binding ◽  
Growth Factor Beta ◽  
Igfbp 3

The IGF axis has been implicated in the pathogenesis of benign prostatic hyperplasia (BPH) via the paracrine action of IGFs and IGF-binding proteins (IGFBPs). In this study, we examined the regulation of cell growth and IGFBP-3 secretion by transforming growth factor-beta (TGF-beta) in prostatic stromal cell (PC-S) cultures from histologically normal tissues and tissues from BPH. PC-S cultures were treated with varying doses of TGF-beta1. Forty-eight hour conditioned media (CM) from these cultures were subjected to Western immunoblotting and ligand blotting for detection and quantification of IGFBPs. IGFBPs-2, -3 and -4 were detected in the CM from normal PC-S cultures. In CM from BPH PC-S, IGFBP-3 levels were 2-fold lower at baseline than in the normal PC-S CM, in addition to the differences in IGFBPs-2 and -5 which we have previously reported. In response to TGF-beta1, a 15-fold increase in the levels of IGFBP-3 was observed in normal PC-S CM, while a mere 2-fold increase was observed in BPH PC-S CM (P<0.001). These findings were confirmed by specific immunoblotting and immunocytochemistry. IGFBP-3 mRNA levels detected by Northern blotting of total RNA extracted from similar cultures showed the induction of IGFBP-3 expression by TGF-beta1 in normal PC-S and its lack of induction in BPH PC-S. Cell growth inhibition in response to TGF-beta1 correlated with the IGFBP-3 concentrations found in CM. Normal PC-S showed a 60% decrease in cell number after 10 days in media with 1 ng/ml TGF-beta1, compared with the untreated control. The decrease in proliferation observed in comparably treated BPH cells was only 20% (P<0.001). In conclusion, BPH PC-S had a reduced IGFBP-3 response to TGF-beta1 and demonstrated decreased TGF-beta1-induced growth inhibition relative to normal PC-S. We hypothesize that in normal PC-S, TGF-beta exerts its anti-proliferative effects by stimulating the production of IGFBP-3, which acts as an inhibitory factor, either by inhibiting IGFs or directly by interacting with cells, and that this process is altered in BPH PC-S.

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